Endoluminal implant with therapeutic and diagnostic capability

ABSTRACT

An apparatus includes an endoluminal implant, a RF coupling coil coupled to the endoluminal implant and a therapeutic transducer electrically coupled to the RF coupling coil and physically coupled to the endoluminal implant. The RF coupling coil supplies electrical power to the therapeutic transducer. The therapeutic transducer has a capability for delivering therapeutic energy to a lumen disposed within the endoluminal implant in response to signals coupled via the RF coupling coil.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a divisional of pending U.S. patent application Ser.No. 09/028,154, filed Feb. 23, 1998 now U.S. Pat. No. 6,231,516.

TECHNICAL FIELD

This invention relates generally to implantable devices, and, moreparticularly, to implantable medical devices having therapeutic ordiagnostic functions within a lumen of an endoluminal implant such as astent or other type of endovascular conduit, and methods related to suchimplantable medical devices.

BACKGROUND OF THE INVENTION

In the 1970s, the technique of percutaneous transluminal coronaryangioplasty (PTCA) was developed for the treatment of atherosclerosis.Atherosclerosis is the build-up of fatty deposits or plaque on the innerwalls of a patient's arteries; these lesions decrease the effective sizeof the artery lumen and limit blood flow through the artery,prospectively causing a myocardial infarction or heart attack if thelesions occur in coronary arteries that supply oxygenated blood to theheart muscles. In the angioplasty procedure, a guide wire is insertedinto the femoral artery and is passed through the aorta into thediseased coronary artery. A catheter having a balloon attached to itsdistal end is advanced along the guide wire to a point where thesclerotic lesions limit blood flow through the coronary artery. Theballoon is then inflated, compressing the lesions radially outwardagainst the wall of the artery and substantially increasing the size ofits internal lumen, to improve blood circulation through the artery.

Increasingly, stents are being used in place of or in addition to PTCAfor treatment of atherosclerosis, with the intent of minimizing the needto repeatedly open an atherosclerotic artery. Although a number ofdifferent designs for stents exist in the prior art, all are generallyconfigured as elongate cylindrical structures that are provided in afirst state and can assume a second, different state, with the secondstate having a substantially greater diameter than the first state. Astent is implanted in a patient using an appropriate delivery system forthe type of stent being implaced within the patient's arterial system.There are two basic types of stents—those that are expanded radiallyoutward due to the force from an inflated angioplasty type balloon, suchas the Palmaz-Schatz stent, the Gianturco-Roubin stent and the Streckerstent, and those that are self expanding, such as the Maass double helixspiral stent, the Nitinol stent (made of nickel titanium memory alloy),the Gianturco stent and the Walistent. Problems with the Maass doublehelix spiral stent and the Nitinol stent have limited their use.

Stents are sometimes used following a PTCA procedure if the artery istotally occluded or if the lesions have occluded a previously placedsurgical graft. Typically, a stent constrained within an introducersheath is advanced to a site within the patient's artery through a guidecatheter. For the balloon expanded type, after the introducer sheath isretracted, a balloon disposed inside the stent is inflated to a pressureranging from about six to ten atmospheres. The force produced by theinflated balloon expands the stent radially outward beyond its elasticlimit, stretching the vessel and compressing the lesion to the innerwall of the vessel. A self expanding stent expands due to spring forcefollowing its implacement in the artery, after a restraining sheath isretracted from the compressed stent, or in the case of the Nitinolversion, the stent assumes its expanded memory state after being warmedabove the transition temperature of the Nitinol alloy (e.g., above 30°C.). Following the expansion process, when the balloon catheter is used,the balloon is removed from inside the stent and the catheter and otherdelivery apparatus is withdrawn. The lumen through the vessel is thensubstantially increased, improving blood flow.

After a stent or other endoluminal device is implanted, a clinicalexamination and either an angiography or an ultrasonic morphologicalprocedure is performed to evaluate the success of the stent emplacementprocedure in opening the diseased artery or vessel. These tests aretypically repeated periodically, e.g., at six-month intervals, sincerestenosis of the artery may occur. Due to the nature of the tests, theresults of the procedure can only be determined qualitatively, but notquantitatively, with any degree of accuracy or precision. It wouldclearly be preferable to monitor the flow of blood through the stentafter its implacement in a vessel, both immediately following thetreatment for the stenosis and thereafter, either periodically or on acontinuous basis. Measurements of volumetric rate and/or flow velocityof the blood through the stent would enable a medical practitioner tomuch more accurately assess the condition of the stent and of the arteryin which the stent is implanted. Currently, no prior art mechanism isavailable that is implantable inside a blood vessel for monitoring bloodflow conditions through a stent.

Following stent implantation, it is difficult to monitor the conditionof the affected area. Stents often fail after a period of time and for avariety of reasons. Several of the causal mechanisms are amenable todrug treatment. It is highly desirable in at least some of these casesto localize the drug treatment to the site of the graft or surgery. Forexample, when thrombus forms in a given area, thrombolytic drugs arecapable of providing significant assistance in resolving the thrombosis,but may present problems such as hemorrhaging, if they also act in otherportions of the patient's body.

SUMMARY OF THE INVENTION

The present invention provides a capability for including a therapeutictransducer together with an endoluminal implant such as a stent or stentgraft. Therapeutic transducers may include ultrasonic, magnetic,iontophoretic, heating or optical devices, which may permit localizeddrug delivery or localized drug activation. Provision is made fordelivering energy to the implanted transducers and for coupling signalsto or from the implanted transducers. The present invention also permitsinclusion of diagnostic transducers together with the endoluminalimplant and allows signals to be transmitted from the diagnostictransducers to an area outside of the patient's body.

The present invention can allow steps that may be taken to restore fullfluid flow through, e.g., a stent that is becoming restricted. In thesecases, it is desirable to initiate treatment before the problem proceedstoo far to be corrected without stent replacement or further PTCAtreatment. Clearly, it would be preferable to be able to monitor thecondition of a stent without resorting to invasive surgical proceduresand without prescribing medication that may not be necessary, so thatthe useful life of the stent may be extended, problems associated stentfailure avoided and so that medications are only prescribed whenrequired by the known condition of the stent and associated vasculature.

Other advantages that may be realized via embodiments of the presentinvention including monitoring of other parameters measurable within astent or other type of endoluminal implant using one or more appropriatesensors or transducers according to embodiments of the presentinvention. For example, monitoring pressure at the distal and proximalends of the lumen in the implant and determining the differentialpressure can provide an indication of fluid velocity through the lumen.Temperature can also be used to monitor fluid flow by applying heat tothe fluid within the lumen and monitoring the rate at which thetemperature of the fluid decreases as the fluid flows through the lumenof the implant. Integrated circuit (IC) transducers are currently knownand available for sensing the levels of many different types ofbiochemical substances, such as glucose, potassium, sodium, chlorideions and insulin. Any of these IC sensors could be provided in anendoluminal implant to monitor these parameters.

Since it is impractical to pass a conductor through the wall of anartery or vessel for long periods of time, use of a conventional sensorthat produces signals indicative of flow through a stent, which must beconveyed through a conductor that extends through the wall of the vesseland outside the patient's body, is not a practical solution to thisproblem. Also, any active flow indicative sensor must be energized withelectrical power. Again, it is not practical to supply power to such asensor through any conductor that perforates the vessel wall or thatpasses outside the patient's body.

In addition to stents, the generic term endoluminal implant encompassesstent grafts, which are also sometimes referred to as “spring grafts.” Astent graft is a combination of a stent and a synthetic graft isendoluminally implanted at a desired point in a vessel. Helically coiledwires comprising the stent are attached to the ends of the syntheticgraft and are used to hold the graft in position. Sometimes, hooks areprovided on the stent to ensure that the graft remains in the desiredposition within the vessel. Clearly, it is advantageous to monitor thestatus of flow and other parameters through a stent graft, just as notedabove in regard to a stent.

Endoluminal implants are used in other body passages in addition toblood vessels. For example, they are sometimes used to maintain an openlumen through the urethra, or through the cervix. A stent placedadjacent to an enlarged prostate gland can prevent the prostate fromblocking the flow of urine through the urethra. Tracheal and esophagealimplants are further examples of endoluminal implants. In these andother uses of endoluminal implants, provision for monitoring parametersrelated to the status of flow and other conditions in the patient's bodyis desirable. Information provided by monitoring such parameters, andlocalized drug delivery or drug activation, can enable more effectivemedical treatment of a patient through use of embodiments of the presentinvention.

Another advantage that may be realized through practice of embodimentsof the present invention is to be able to activate a therapeutic deviceon the stent or stent graft that would allow the physician to activatedrugs known to be effective in preventing further tissue growth withinthe stent or stent graft in situations where it is determined thattissue ingrowth is threatening the viability of a stent or stent graft.Again, the therapeutic device should be able to be supplied withelectrical power from time to time from a location outside the patient'sbody.

Yet another advantage that may be realized through practice of thepresent invention is the treatment of tumors or organs that aredownstream of the blood vessel that includes a stent that is coupled toa transducer. The transducer may be remotely activated to facilitatelocalized drug delivery or to provide other therapeutic benefits.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing aspects and many of the attendant advantages of thisinvention will become more readily appreciated as the same becomesbetter understood by reference to the following detailed description,when taken in conjunction with the accompanying drawings, wherein:

FIG. 1 is a block diagram according to the invention showing a firstembodiment of an implantable electronic circuit for coupling electricalsignals to or from a selected transducer of a plurality of transducers.

FIG. 2 is a block diagram of a second embodiment of an implantableelectronic circuit for coupling electrical signals to or from atransducer using separate multiplexers for transmit and receivefunctions.

FIG. 3 is a block diagram of a third embodiment of an implantableelectronic circuit for coupling electrical signals to or from atransducer using separate multiplexers and amplifiers for transmit andreceive functions.

FIG. 4 is a block diagram of a fourth embodiment of an implantableelectronic circuit for coupling electrical signals to or from atransducer that employs a local transmitter to excite a selectedtransducer, and a modulator/transmitter for transmitting signals fromthe transducers.

FIG. 5 is a block diagram of a fifth embodiment of an implantableelectronic circuit for coupling electrical signals to or from atransducer, where one transducer is selected for transmitting andreceiving, and a modulator/transmitter is used for transmitting thesignal produced by the receiving transducer.

FIG. 6 is a block diagram of a sixth embodiment of an implantableelectronic circuit for monitoring the status of a stent or stent graft,wherein one of a plurality of transducers is selectively coupled to amodulator/transmitter or a receiver.

FIG. 7 is a cross-sectional view of a radio frequency (RF) coupling coilin a stent that is implanted in a blood vessel, and an external coilthat is electromagnetically coupled to the RF coupling coil.

FIG. 8 is a cross-sectional view of a RF coupling coil in a stentimplanted in a blood vessel, and includes a block that represents animplanted coil, which is electromagnetically coupled to the RF couplingcoil.

FIG. 9 is a side elevational view of a woven mesh RF coupling coil thatcomprises a wall of a stent.

FIG. 10 is a cut-away side elevational view of a further embodiment ofan external coil and a side elevational view of a blood vessel in whicha stent is implanted that includes a saddle-shaped RF coupling coilintegrated within the wall of the stent.

FIG. 11A is a side elevational view (showing only the foreground) of aportion of a metal tube-type stent with nonconductive weld joints,illustrating a RF coupling coil wrapped around the stent in apre-expansion configuration.

FIG. 11B is a side elevational view (showing only the foreground) of aportion of a zigzag wire stent with non-conductive joints, illustratinga RF coupling coil wrapped around the stent in a pre-expansionconfiguration.

FIG. 12 is a cut-away view of a portion of a limb showing a stentimplanted at a substantial depth within a blood vessel, and an externalcoupling coil that encompasses the stent.

FIG. 13 is a side elevational schematic view of a dual beam conformalarray transducer on an expandable carrier band for use in a stent.

FIG. 14 is an end elevational view of the conformal array transducer ofFIG. 13, within a stent.

FIG. 15 is a plan view of the conformal array transducer shown in FIGS.13 and 14, cut along a cut line to display the dual conformal arrays ina flat disposition.

FIG. 16A is a cross-sectional side view of a portion of a stent in whichare disposed transversely oriented transducers for monitoring flow usingcorrelation measurements.

FIG. 16B is a transverse cross-sectional view of the stent andtransversely oriented transducers shown in FIG. 16A.

FIG. 17 is an enlarged partial transverse cross-sectional view of thelayers comprising the conformal array transducer disposed on a stentwithin a blood vessel.

FIG. 18 is an enlarged partial cross-sectional side view of atilted-element transducer array disposed within a stent.

FIG. 19A is an isometric view of an integrated circuit (IC) transducermounted on a tubular stent.

FIG. 19B is an enlarged partial cross-sectional side view of theimplantable IC transducer mounted on the tubular stent.

FIG. 19C is an isometric view of the implantable IC transducer mountedon a woven mesh stent.

FIG. 19D is an enlarged partial cross-sectional side view of theimplantable IC transducer mounted on the woven mesh stent.

FIG. 20 is a side elevational schematic view showing an IC strain sensorand sensing filaments disposed on a stent.

FIG. 21A is side elevational schematic view of a stent outline showing adeposit and ingrowth IC sensor and sensing filament.

FIG. 21B is a cross-sectional view of a lumen of the stent in FIG. 21A,illustrating fatty tissue ingrowth.

FIG. 22 is side elevational view of a portion of a branching artery inwhich a stent graft that is used for providing therapeutic functions isimplanted.

FIG. 23 illustrates an ultrasonic transducer configuration integratedwith a stent or stent graft.

FIG. 24 illustrates an embodiment of a dual frequency ultrasonictransducer.

FIG. 25 illustrates one embodiment of a coil integrated into a stent.

FIG. 26 illustrates another embodiment of a coil integrated into astent.

FIG. 27 illustrates an embodiment of an iontophoretic system for localdrug delivery.

FIG. 28 illustrates an embodiment wherein light emitting transducers arecoupled to a stent.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is employed for providing therapeutic functionsproximate to an endoluminal implant. As used herein and in the claimsthat follow, the term endoluminal implant broadly encompasses stents,stent grafts (sometimes referred to as “spring grafts”) and other typesof devices that are inserted into a lumen or body passage and moved to adesired site to provide a structural benefit to the lumen. To simplifythe disclosure of the present invention, most of the followingdiscussion is directed to embodiments comprising a stent.

In one embodiment, parameters are monitored via implanted diagnostictransducers, where the monitored parameters are directed to determiningthe status of the fluid flow through the endoluminal implant, andtherapeutic transducers may be activated in response to the datacollected from the implanted diagnostic transducers. For example, therate or velocity of fluid flow through a body passage in which the stenthas been positioned can be monitored to determine the extent of tissuegrowth or fatty deposits in a blood vessel in which the stent has beenimplanted to treat atherosclerosis. By monitoring these parameters,which are indicative of blood flow through the lumen of the stent andthe blood vessel in which it is implanted, a medical practitioner canevaluate the need for further treatment or determine whether restenosishas occurred, and can locally activate drugs to control restenosis whenit is determined to have occurred. This may be possible withoutadditional surgery and without some of the complications associated withsystemic administration of drugs. Moreover, other physical andbiological parameters can be monitored using one or more appropriatesensors attached to a stent.

When implanted therapeutic transducers are to be activated for anextended period of time or following an extended delay, the stent willlikely need to receive electrical power from an external source toenergize the implantable electronic circuitry used to activate theimplanted therapeutic transducers. Similarly, when the status of fluidflow through a stent that has been implanted in a patient's vascularsystem (or some other parameter that is sensed proximate the stent) isto be monitored for an extended period or following an extended delay,the implanted circuitry associated with the stent will likely need toreceive electrical power from an external source. This power may also beneeded to convey data indicating the status of fluid flow (or otherparameter) from the implanted stent to a monitoring device that isdisposed outside the patient's body. In many cases, it may be desirableto monitor one or more parameters at multiple stents or at multiplelocations on a single stent, or to provide therapeutic functions at morethan one stent or to multiple locations within or associated with onestent. Thus, the specific transducer employed to provide a therapeuticfunction or transducer or sensor employed to monitor a desired parametermust be selectable so that the data signal indicating the parameter canbe transmitted outside the patient's body. However, in some cases, onlya single transducer (which may be operable without any implanted controlelectronics) may be required to provide a therapeutic function or tomonitor a parameter such as fluid volumetric flow or velocity, which isindicative of the internal condition of the stent and of the bloodvessel in which it is implanted.

FIG. 1 illustrates a first embodiment of an implantable electroniccircuit for providing one or more therapeutic functions or formonitoring one or more parameters, applicable to the situation in whichn transducers 44-46 are included on one or more stents implanted in thepatient's body. Variations of the implantable electronic circuit shownin FIG. 1 are discussed below to accommodate specific conditions. Inaddition, other embodiments of implantable electronic circuits areillustrated in FIGS. 2 through 6. These embodiments, like that of FIG.1, are useful for providing power to transducers that providetherapeutic functions, e.g., that activate drugs or that assist inlocalized drug delivery, or that monitor fluid flow or velocity througha stent and also for transmitting data signals from the transducers tolocations outside a patient's body, e.g., to an external remotemonitoring console. Some of these implantable electronic circuits arebetter suited for certain types of therapy or measurements than others,and again, variations in the implantable electronic circuits arediscussed below, where appropriate, to explain these distinctions.Examples of implantable telemetry systems are discussed in ATelemetry-Instrumentation System For Monitoring Multiple SubcutaneouslyImplanted Glucose Sensors by M. C. Shults et al., IEEE Trans. Biomed.Eng., Vol. 41, No. 10, October 1994, pp. 937-942 and in IntegratedCircuit Implantable Telemetry Systems by J. W. Knutti et al., Eng. inMed. and Bio. Magazine, March 1983, pp. 47-50.

Each of the implantable electronic circuits shown in FIGS. 1 through 6are intended to be implanted within the patient's body and left in placeat least during the period in which a therapeutic function may be neededor the flow conditions through one or more stents or other parametersare monitored. Although separate functional blocks are illustrated fordifferent components of the implantable electronic circuits in theseFigures, any of the implantable electronic circuits can be implementedin one or more application specific integrated circuits (ASICs) tominimize size, which is particularly important when the implantableelectronic circuits are integral with a stent. The implantableelectronic circuits can be either included within the wall of a stent,or may be simply implanted adjacent to blood vessel(s) in which thestent(s) is/are disposed. However, if not integral with the stent, theimplantable electronic circuits must be electromagnetically coupled tothe transducers, since it is impractical to extend any conductor througha wall of the blood vessel in which a stent is implanted, to couple tocircuitry disposed outside the blood vessel. Therefore, in someembodiments, the implantable electronic circuits are integral with thestent so that they are implanted, together with the stent, inside theblood vessel.

Each of the implantable electronic circuits shown in FIGS. 1 through 6includes a RF coupling coil 30, which is coupled via lines 34 and 36 toa RF-to-DC power supply 32. In one embodiment, the RF coupling coil 30is part of the expandable structure of the stent body or may instead beadded to a stent, for example, by threading an insulated wire throughthe expandable wall of a stent. In some embodiments, the RF couplingcoil 30 comprises a helical coil or saddle-shaped coil, as explained ingreater detail below. The RF-to-DC power supply 32 rectifies and filtersa RF excitation signal supplied from an external source to the RFcoupling coil 30, providing an appropriate voltage DC power signal forthe other components of the implantable electronic circuits illustratedin these Figures. In the simplest case, the RF-to-DC power supply 32would only require rectifiers and filters as appropriate to provide anyneeded positive and negative supply voltages, +V_(S) and −V_(S).

However, it is also contemplated that the RF-to-DC power supply 32 mayprovide for a DC-to-DC conversion capability in the event that theelectromagnetic signal coupled into the RF coupling coil 30 is too weakto provide the required level of DC voltage for any component. Thisconversion capability would increase the lower voltage produced by thedirect coupling of the external RF excitation signal received by the RFcoupling coil 30, to a higher DC voltage. Details of the RF-to-DC powersupply 32 are not shown, since such devices are conventional. It is alsocontemplated that it may be necessary to limit the maximum amplitude ofthe RF input signal to the RF-to-DC power supply 32 to protect it or sothat excessive DC supply voltages are not provided to the othercomponents.

Alternatively, each component that must be provided with a limited DCvoltage supply may include a voltage limiting component, such as a zenerdiode or voltage regulator (neither shown). In another embodiment, theRF coupling coil 30 and the RF-to-DC power supply 32 of FIGS. 1 through6 may be replaced by a hard-wired connection to supply DC or AC power inapplications where the implant is needed for a relatively shortduration, where the inconvenience of the cables supplying the power istolerable and the risk of infection is manageable. An example of ahard-wired transcutaneous connection for chronic implants is describedin Silicon Ribbon Cables For Chronically Implantable MicroelectrodeArrays by J. F. Hetke et al., IEEE Trans. Biomed. Eng., Vol. 41, No. 4,April 1994, pp. 314-321.

The RF-to-DC power supply 32 may include a battery or a capacitor forstoring energy so that it need not be energized when providing atherapeutic function or monitoring the flow status, or at least, shouldinclude sufficient storage capability for at least one cycle ofreceiving energy and transmitting data relating to the parameter beingmonitored. Neither a battery nor power storage capacitor are illustratedin the Figures, since they are conventional also.

Implantable electronic systems using battery power may only require theability to receive data and control signals and may include the abilityto transmit signals. As a result, they do not necessarily require accessto the skin, which access facilitates efficient coupling of powersignals. A battery-powered system may result in a very compactimplantable system. Alternatively, a battery-powered system that also iscapable of recharging the battery via power signals coupled through animplanted coil can permit continuing treatment without requiring that aphysician be present throughout the treatment or requiring the patientto be in the medical facility.

An element that is common to each of the implantable electronic circuitsshown in FIGS. 1 through 3 is a RF decode section 40, which is used forgenerating control signals that are responsive to information encoded inthe external RF excitation signal received by the RF coupling coil 30.This information can be superimposed on the RF excitation signal, e.g.,by amplitude or frequency modulating the signal.

In regard to the implantable electronic circuits shown in FIGS. 1through 3, when used for monitoring fluid velocity or flow, the RFexcitation frequency is the same as the frequency used to provide energyfor therapeutic functions (e.g., localized drug activation) or to excitea selected ultrasonic transducer to produce an ultrasonic wave thatpropagates through a lumen of the stent being monitored and forconveying data from the transducer 44-46 that receives the ultrasonicwaves. This approach generally simplifies the implantable electroniccircuitry but may not provide optimal performance.

Therefore, FIGS. 4 and 5 disclose implantable electronic circuitry inwhich the RF excitation frequency used to provide power to the RF-to-DCpower supply 32 and to provide control signals to the RF decode section40 is decoupled from the frequency that is used for exciting thetransducers 44-46 and modulating any data that they provide fortransmission to a point outside the patient's body. Although other typesof transducers 44-46 may be employed that are energized with a RFexcitation frequency, such as surface acoustic wave transducers that areused for sensing chemical substances, many transducers 44-46 onlyrequire a DC voltage to sense a desired parameter such as pressure ortemperature or to provide a static magnetic field, heat or light fortherapeutic purposes.

Implantable Electronic Circuits

Referring now to FIG. 1, a line 36 from the RF coupling coil 30 iscoupled to a multiplexer (MUX) 38 to convey signals from a selected oneof a plurality of n transducers 44-46 (which are disposed at differentpoints on a stent) that are coupled to the MUX 38. To select thetransducer 44-46 that will provide a therapeutic function or a datasignal related to a parameter at a specific location on a stent, the RFdecode section 40 provides a control signal to the MUX 38 through MUXcontrol lines 42. The control signal causes the MUX 38 to select aspecific transducer 44-46 that is to be excited by the RF signalreceived by the RF coupling coil 30 and further, causes the MUX 38 toselect the transducer 44-46 that will provide the data signal fortransmission outside the patient's body (or at least outside the bloodvessel in which the stent is disposed) via the RF coupling coil 30.

In addition to ultrasonic transducers 44-46, the implantable electroniccircuit shown in FIG. 1 can also be used in connection with pressuretransducers 44-46. For ultrasonic transducers 44-46, the circuit isperhaps more applicable to the Doppler type for use in monitoring fluidvelocity through a stent. If a single-vessel pulse Doppler transducer44-46 is used, the same transducer 44-46 can be used for bothtransmission and reception of the ultrasonic wave, thereby eliminatingthe need for the MUX 38. In the event that the transducers 44-46 shownin FIG. 1 are used for transit time flow measurements, it will normallybe necessary to use the MUX 38 to switch between the transducer 44-46used for transmitting the ultrasonic wave and that used to receive theultrasonic wave.

For a single-vessel transit time measurement, a pair of opposedtransducers 44-46 that are disposed on opposite sides of the stent aretypically used. In order to acquire bi-directional fluid flow data, thedirection of the ultrasound wave propagation must be known, i.e., thedirection in which the ultrasound wave propagates relative to thedirection of fluid flow through the vessel. In this case, the MUX 38 isrequired. However, for single-vessel applications in which the fluidflow is in a single known direction, the transducers 44-46 that aredisposed on opposite sides of the stent can be electrically coupled inparallel or in series, eliminating any requirement for the MUX 38. TheRF-to-DC power supply 32 and the RF decode section 40 could also then beeliminated, since the retarded and advanced transit time signals aresuperimposed on the same RF waveform transmitted by the RF coupling coil30 to a location outside the patient's body (or outside the blood vesselin which the stent is disposed, if an internal coil is implantedadjacent the blood vessel near where the stent is implanted). Althoughthis modification to the implantable electronic circuit shown in FIG. 1would not permit the direction of fluid flow through a stent to bedetermined, the retarded and advanced transit time signals interfereover time, and their interference can be used to estimate the magnitudeof fluid flow through the stent.

In some applications, a single transducer 44-46 or group of transducers44-46 may be employed, in which case the implantable electronic circuitof FIG. 1 may be simplified by coupling the transducer(s) 44-46 directlyto the RF coupling coil 30 and eliminating the MUX 38. In thisembodiment, the RF decode section 40 and the RF-to-DC power supply 32are optional; when the transducer, for example, requires DC excitationor other excitation different than that which may be provided directlyvia the RF coupling coil 30, the RF-to-DC power supply 32 may bedesirable. Similarly, some sensors may have more than one function andthen the RF decode section 40 may also be desirable. Similarly, theimplantable electronic circuits of FIGS. 2 through 6 may be modified toprovide the desired or required functionality.

In FIG. 2, an implantable electronic circuit is shown that uses atransmit multiplexer (TX MUX) 50 and a receive multiplexer (RX MUX) 54.In addition, a transmit (TX) switch 48 and a receive (RX) switch 52couple line 36 to the TX MUX 50 and the RX MUX 54, respectively. The RFdecode section 40 responds to instructions on the signal received fromoutside the patient's body by producing a corresponding MUX controlsignal that is conveyed to the TX MUX 50 and the RX MUX 54 over MUXcontrol lines 56 to select the desired transducers 44-46.

When ultrasonic signals are being transmitted by one of the selectedtransducers 44-46, the TX switch 48 couples the RF excitation signalreceived by the RF coupling coil 30 to the transducer 44-46 that istransmitting the ultrasonic signal, which is selected by the TX MUX 50.The TX switch 48 is set up to pass excitation signals to the selectedtransducer 44-46 only if the signals are above a predetermined voltagelevel, for example, 0.7 volts. Signals below that predetermined voltagelevel are blocked by the TX switch 48. Similarly, the RX switch 52couples the transducer 44-46 selected by the RX MUX 54 to the RFcoupling coil 30 and passes only signals that are below thepredetermined voltage level, blocking signals above that level.Accordingly, the RF signal used to excite a first transducer 44-46selected by the TX MUX 50 passes through the TX switch 48 and the loweramplitude signal produced by a second transducer 44-46 selected by theRX MUX 54 in response to the ultrasonic signal transmitted through thestent is conveyed through the RX MUX 54 and the RX switch 52 andtransmitted outside the patient's body through the RF coupling coil 30.

The implantable electronic circuit shown in FIG. 3 is similar to that ofFIG. 2, but it includes a transmit amplifier (TX AMP) 58 interposedbetween the TX switch 48 and the TX MUX 50, and a receive amplifier (RXAMP) 60 interposed between the RX MUX 54 and the RX switch 52. The TXAMP 58 amplifies the excitation signal applied to the transducer 44-46selected by the TX MUX 50 for producing the ultrasonic wave that ispropagated through the interior lumen of a stent. Similarly, the RX AMP60 amplifies the signal produced by the transducer 44-46 selected by theRX MUX 54 before providing the signal to the RX switch 52 fortransmission outside the patient's body (or at least, outside the bloodvessel in which the stent is implanted). Again, the implantableelectronic circuit shown in FIG. 3 is most applicable to transit timeflow measurements and employs the same frequency for both the RFexcitation signal that supplies power to the RF-to-DC power supply 32and the signal applied to a selected one of the transducers 44-46 togenerate the ultrasonic wave propagating through the stent.

In contrast to the implantable electronic circuits shown in FIGS. 1through 3, the implantable electronic circuit shown in FIGS. 4 through 6enables the RF excitation frequency applied to the RF-to-DC power supply32 to be decoupled from the frequency of the signal applied to exciteany selected one of the transducers 44-46. Similarly, the signalproduced by the transducer 44-46 receiving ultrasonic waves propagatingthrough the stent is at a different frequency than the RF excitationfrequency applied to the RF-to-DC power supply 32. In FIG. 4, atransmitter (XMTR) 62 and a receive modulator/transmitter (RX MOD/XMTR)64 are coupled to and controlled by a RF decode/control section 66. TheRF decode/control section 66 determines when the excitation frequency isgenerated for application to a selected transmit transducer 44-46 andwhen the signal produced by the transducer selected to receive theultrasonic wave is used for modulating the RF signal applied to the RFcoupling coil 30. An advantage of this approach is that the RF powerdelivered to the RF coupling coil 30 is at an optimal frequency forpenetration through the patient's body, thereby improving the efficacywith which the RF energy couples to a specific depth and location withinthe body. Another reason for using this approach is to enable selectionof a particular frequency as necessary to comply with radio frequencyallocation bands for medical equipment. Similarly, the frequency appliedto any selected transducers 44-46 to stimulate their production ofultrasonic waves can be optimal for that purpose. Assuming that the twofrequency bands, i.e., the RF excitation frequency band for the signalapplied to the RF-to-DC power supply 32 and the frequency band of thesignals applied to excite the transducers 44-46, are sufficientlyseparated, the RF power delivery can occur simultaneously with theexcitation of a selected transducer 44-46 and the reception of theultrasonic waves by another selected transducer 44-46. Accordingly, moreRF power can be coupled into the system from the external source than inthe implantable electronic circuits shown in FIGS. 1 through 3. In someembodiments, including those where a battery is used, the RFdecode/control section 66 may also include a RF oscillator for providingthe RF signals to the transducers 44-46 or for coupling signals from thetransducers 44-46 to external electronic apparatus.

The control signals that are supplied to the RF decode/control section66 via the RF coupling coil 30 can be conveyed using nearly any kind ofmodulation scheme, e.g., by modulating the RF excitation that powers thedevice, or by sending a control signal on a separate and distinct RFfrequency. Also, the signals that are received from the transducer 44-46in response to the ultrasonic wave that is propagated through the stentcan be transmitted through the RF coupling coil 30 at a differentfrequency than the incoming excitation frequency, thereby reducing thelikelihood of interference between the power supply and data signaltransmission functions.

The implantable electronic circuit shown in FIG. 4 is applicable totransit time flow measurements in which pairs of transducers 44-46 areselected for transmitting and receiving the ultrasonic wave thatpropagates through the one or more stents on which the transducers 44-46are installed. The RF decode/control section 66 can be employed tocontrol the TX MUX 50 and the RX MUX 68 to interchange the transducers44-46 used for transmission and reception of the ultrasonic wave onsuccessive pulses. Using this technique, the direction of the ultrasonicwave propagation through the stent is changed on alternating pulses ofultrasonic waves, enabling transit time difference information to begathered without requiring further multiplexer programming informationto be transmitted between successive ultrasonic wave pulses. Thisapproach greatly improves the data gathering efficiency of theimplantable electronic circuit shown in FIG. 4 compared to thepreviously described implantable electronic circuits of FIGS. 1 through3.

To further improve the implantable electronic circuit shown in FIG. 4for use in sensing fluid velocity through a stent using a Dopplertechnique, the modification shown in FIG. 5 is made. In FIG. 5, a TX/RXswitch 72 is added so that the implantable electronic circuit transmitsand receives through the same transducer 44-46. As a result, theseparate transmit 50 and receive 54 multiplexers of FIG. 4 are notrequired. Instead, the MUX 38 is used to select the specific transducer44-46 for receiving the RF excitation signal produced by the XMTR 62 sothat the transducer 44-46 produces an ultrasonic wave and then receivesthe echo from fluid flowing through the stent to produce a received datasignal that is output through the RX MOD/XMTR 64. The TX/RX switch 72prevents the signal applied by the TX AMP 58 from overdriving the inputto the RX AMP 60, effectively isolating the RX AMP 60 during the timethat the RF signal is applied to the transducer 44-46 to excite it sothat it produces the ultrasonic wave. However, the echo signal receivedby the transducer 44-46 is allowed to reach the RX AMP 60 when the TX/RXswitch 72 changes state (from transmit to receive). Generally, theimplantable electronic circuit shown in FIG. 5 has the same benefits asdescribed above in connection with the implantable electronic circuitshown in FIG. 4. The RF decode/control section 66 responds to theinformation received from outside the patient's body that determineswhich one of the transducers 44-46 is selected at any given time byproducing an appropriate MUX control signal that is supplied to the MUX38 over the MUX control lines 56.

It is also contemplated that the RF decode/control section 66 may causethe MUX 38 to select a different transducer 44-46 forproducing/receiving the ultrasonic waves after a predefined number oftransmit/receive cycles have elapsed. For example, a differenttransducer 44-46 may be selected after eight cycles have beenimplemented to transmit an ultrasonic wave into the stent and to receiveback the echoes from the fluid flowing through the stent. By collectingdata related to the status of flow through a stent in this manner, itbecomes unnecessary to send programming information to the RFdecode/control section 66 after each cycle of a transmission of theultrasonic wave into the fluid in the stent and reception of the echo.Also, by carrying out a predefined number of transmit/receive cycles forthe given transducer 44-46 that has been selected by the MUX 38 andaveraging the results, a more accurate estimate of fluid velocitythrough the stent can be obtained than by using only a singletransmission and reception of an ultrasonic wave. Since the signalrequired to instruct the RF decode/control section 66 to change to thenext transducer 44-46 is only required after the predefined number ofcycles has been completed, the data gathering efficiency of theimplantable electronic circuit is improved.

As noted above, the transducers 44-46 shown in FIGS. 1 through 5 neednot be ultrasonic transducers; FIG. 6 illustrates an electronic circuitthat is particularly applicable for use with transducers 44-46comprising pressure sensors. Silicon pressure sensors designed to beinstalled on the radial artery are available from the AdvancedTechnologies Division of SRI of Palo Alto, Calif. Such pressure sensorscould be disposed within the wall of a stent to sense the pressure offluid flowing through the stent at one or more points. The MUX 38 isused for selecting a specific pressure transducer to provide a datasignal that is transmitted to the outside environment via the RFcoupling coil 30. In the implantable electronic circuit shown in FIG. 6,a modulator/transmitter (MOD/XMTR) 70 receives the signal from thetransducer 44-46 selected by the MUX 38 in response to the MUX selectionsignal provided over the MUX control lines 56 from the RF decode/controlsection 66 and, using the signal, modulates a RF signal that is suppliedto the RF coupling coil 30. The RF signal transmitted by the RF couplingcoil 30 thus conveys the data signal indicating pressure sensed by theselected transducer 44-46. In many cases, it will be preferable tomonitor the pressure at the upstream and downstream ends of a stent inorder to enable the differential pressure between these ends to bedetermined. This differential pressure is indicative of the extent towhich any blockage in the lumen of the stent is impeding fluid flowingthrough the lumen. In most cases, parameters such as fluid flow orvelocity are better indicators of the status of flow through the stent.

RF Coupling Coil and External Coil Embodiments

FIGS. 7 through 12 illustrate details of several different embodimentsfor the RF coupling coil 30 that is part of the stent implanted within apatient's body. The RF coupling coil 30 is for receiving RF energy toprovide power for the implantable electronic circuits of FIGS. 1 through6 and for transmitting data relating to the condition of flow and/orother parameter(s) sensed by transducers coupled to one or more stentsthat have been installed within the patient's vascular system.Optimization of RF coupling between the RF coupling coil 30 on the stentand an external coil is partially dependent upon the propagationcharacteristics of the human body. Since body tissue is largely water,the relative dielectric constant of mammalian soft tissues isapproximately equal to that of water, i.e., about 80. Also, thepermeability of body tissue is approximately equal to one, i.e., aboutthat of free space. The velocity of propagation of a RF signal throughthe body is proportional to the inverse square root of the dielectricconstant and is therefore about 11% of the velocity of the signal infree space. This lower velocity reduces the wavelength of the RF signalby an equivalent factor. Accordingly, the wavelength of the RF signaltransferred between the implanted RF coupling coil on a stent and theexternal coil would be a design consideration if the separation distancebetween the two is approximately equal to or greater than one-quarterwavelength. However, at the frequencies that are of greatest interest inthe present invention, one-quarter wavelength of the RF coupling signalshould be substantially greater than the separation distance between theRF coupling coil 30 on the stent and the external coil.

One method for optimizing coupling between an implanted coil and a coilthat is external to the body is described in High-EfficiencyCoupling-Insensitive Transcutaneous Power And Data Transmission Via AnInductive Link by C. M. Zierhofer and E. S. Hochmair, IEEE Trans.Biomed. Eng., Vol. 37, No. 7, July 1990, pp. 716-722. This approachallows the frequency of the signal linking the implanted and externalcoils to vary in response to the degree of coupling between the twocoils. Other methods are suitable for coupling signals between the twocoils as well.

When the implantable electronic circuit includes the RF coupling coil 30and a transducer 44-46, but does not include active electroniccircuitry, the external system (e.g., external power supply and patientmonitoring console 100, FIG. 8, below) senses a parameter related to theelectrical input impedance of the external coil. When the external andinternal coils are aligned, the inductance and the resistance of theexternal coil are maximized. The frequency of the signal that is usedfor adjusting the alignment may be different than the frequency that isused to provide electrical signals to the transducer.

The implantable electronic circuit may include an additional componentto facilitate sensing of alignment between the two coils. For example, ametal disc in the implant may be detected and localized by inducing aneddy current in the disc. The external power supply and patientmonitoring console may then detect the magnetic field generated by theeddy current in the disc, much as a metal detector operates. Usingdifferent frequencies for the location and therapeutic functions mayavoid energy losses caused by the eddy currents.

When the implantable electronic circuitry does include active electroniccircuitry, a circuit may be included with the therapeutic transducer andRF coupling coil that measures the amplitude of the signal from theexternal power supply and patient monitoring console that is induced inthe RF coupling coil. A signal is transmitted from the implantableelectronic circuitry to the external power supply and patient monitoringconsole, where a display provides an indication of the coupling. Theoperator may adjust the position of the external coil to optimizecoupling between the two coils.

The penetration of RF fields in the human body has been studiedextensively in conjunction with magnetic resonance imaging (MRI)systems. RF attenuation increases with frequency, but frequencies ashigh as 63 MHz are routinely used for whole-body imaging, although someattenuation is observed at the center of the torso at this upperfrequency limit. In addition, MRI safety studies have also provided abasis for determining safe operating limits for the RF excitation thatdefine the amplitude of excitation safely applied without harm to thepatient.

It is contemplated that for stent implants placed deep within the torsoof a patient, RF excitation and frequencies used for communicating datarelated to the fluid flow through a stent and/or other parameters sensedproximate the stent can be up to about 40 MHz, although higherfrequencies up to as much as 100 MHz may be feasible. At 40 MHz, thewavelength of the RF excitation signal in tissue is about 82 cm, whichis just that point where wavelength considerations become an importantconsideration. For shallow implants, RF excitation at a much higherfrequency may be feasible. For example, to provide energy to stents thatare disposed within a blood vessel only a few millimeters below theepidermis and to receive data from transducers associated with suchstents, excitation frequencies in the range of a few hundred MHz may beuseful. The dielectric properties of tissue have been studied to atleast 10 GHz by R. Pethig, Dielectric and Electronic Properties ofBiological Materials, Wiley Press, Chichester, 1979 (Chapter 7). Basedon this study, no penetration problems are anticipated in the frequencyrange of interest. The relative dielectric constant of tissue decreasesto about 60 at a frequency of 100 MHz and is about 50 at 1 GHz, but thisparameter has little effect on power/data signal coupling.

An external coil 90 and a RF coupling coil 30A shown in FIG. 7 representone embodiment of each of these components that can be used for couplingelectrical energy and conveying data signals across a skin interface 102for applications in which the RF coupling coil 30A is implantedrelatively close to the surface 102 of the skin. For example, the RFcoupling coil 30A and the external coil 90 may provide, via magneticflux lines 112, the coupling required for a system used to monitor astent implanted in an artery near the skin surface 102. A winding 92 iswrapped around a core 94 forming the external coil 90 and each end ofthe winding 92 is coupled to a power source through a cable 98.

Although the external coil 90 and the RF coupling coil 30A need not beidentical in size, it is generally true that coupling will be optimal ifthe two devices are of approximately the same dimensions and if thelongitudinal axis of the external coil 90 is generally adjacent andparallel to that of the RF coupling coil 30A. By observing the strengthof the signal transmitted from the RF coupling coil 30A, it should bepossible to position the external coil 90 in proper alignment with theRF coupling coil 30A so that the efficiency of the magnetic couplingbetween the two is optimized.

To function as the core 94 for the external coil 90, the material usedshould have a relatively high magnetic permeability, at least greaterthan one. Although ferrite is commonly used for core materials, sinteredpowdered iron and other alloys can also be used. Since the magneticcharacteristics of such materials are generally conventional, furtherdetails of the external coil 90 and the core 94 are not provided.

A housing 96 on the external coil 90 provides RF shielding againstelectromagnetic interference (EMI). In one embodiment, the housing 96for the external coil 90 is conductive, grounded and surrounds theexternal coil 90 except where the surfaces of the generally “C-shaped”core 94 are opposite the RF coupling coil 30A. The RF shield comprisingthe housing 96 is attached to an internal braided shield 99 of the cable98. Inside the power supply and patient monitoring console (not shown inFIG. 7) to which the cable 98 is coupled, the shield 99 is connected toground. The RF shield on the external coil 90, along with shieldsprovided around transducers 44-46 on the stent 106, minimizes externalEMI radiation due to the use of the present invention within a patient'sbody.

For the embodiment shown in FIG. 7, the external coil 90 is magneticallycoupled to a spiral winding 108 in the stent 106 that is implanted in ablood vessel 107. The spiral winding 108 comprises the RF coupling coil30A for the stent 106 and the opposite ends of the spiral winding 108are coupled to an electronic circuit 110, which may comprise any of theimplantable electronic circuits described above in connection with FIGS.1 through 6. Not shown in FIG. 7 are the one or more transducers 44-46that are included within the stent 106 to monitor one or moreparameters.

The RF coupling coil 30A used in the stent 106 may be either an integralpart of the stent 106, or it may instead comprise a separate RF couplingcoil 30A that is wound around or through the structure comprising thewall of the stent 106. To function within the body of a patient, thestent 106 must be able to bend and flex with movement of the body, yetmust have sufficient surface area and hoop strength to compress theatheriosclerotic material that is inside the blood vessel wall radiallyoutward and to support the vessel wall, maintaining the lumen crosssection. Several manufacturers offer stent designs, each fabricated fromwire, bent back and forth in a periodically repeating “S” shape orzigzag configuration, forming a generally cylindrical tube. Such stentsare considered ideal for use in practicing the present invention, sincethe wire comprising the wall of the stent 106 can be used for the RFcoupling coil 30A. Examples of such stents are the ANGIOSTENT stent madeby AngioDynamics, the stent sold by Cordis Corporation, the CARDIOCOILstent produced by Instent and the WIKTOR stent from MedtronicCorporation.

FIG. 8 illustrates another embodiment in which an implanted coil 90Adisposed outside the blood vessel 107 adjacent to an implanted stent106A is electromagnetically coupled through magnetic flux lines 112 tothe stent 106A using a plurality of electrically isolated and separatehelical windings 109A, 109B, 109C, 109D and 109E forming a woven meshcomprising the wall of the stent 106A. Not shown are the implantableelectronic circuitry and the transducers 44-46 that are coupled to thewindings comprising a RF coupling coil 30B, however, it will beunderstood that any of the implantable electronic circuits shown inFIGS. 1 through 6, discussed above, can be used for this purpose.However, by using electrically isolated and separate windings 109A-E forthe RF coupling coil 30B, it is possible to avoid multiplexing thesignals from each different transducer 44-46 used in the stent 106A,since each transducer 44-46 (or sets of transducers 44-46) can transmitdata over its own winding and separately receive an excitation signalfrom the implanted coil 90A. This figure shows the implanted coil 90Acoupled to an external power source and monitor through a cable 98A. Thecable 98A can either penetrate the dermal layer of the patient's body,passing to the outside environment, or alternatively, may itself beelectromagnetically coupled to an external coil, such as the externalcoil 90 shown in FIG. 7. When the cable 98A from the implanted coil 90Apenetrates the dermal layer 102, it is likely that the parameters beingsensed by the stent 106A will only need to be monitored for a relativelyshort time, so that the implanted coil 90A can be removed from thepatient's body after the need to monitor the parameters is satisfied. Anadvantage of the embodiment shown in FIG. 8 is that when the stent 106Ais implanted deep within the patient's body, it can be readily energizedand the data that it provides can be more efficiently received outsidethe body by using the implanted coil 90A as an interface, eitherdirectly coupled through the skin 102 or magnetically coupled through anexternal coil.

Stents comprising a woven mesh of fine helical wires are available fromcertain stent manufacturers. The woven mesh provides the required hoopstrength needed to support the wall of a blood vessel after the stent isimplanted and expanded or allowed to expand. To maintain the requiredflexibility for the stent, the wires comprising the woven mesh of suchstents are not joined at the intersection points. An example is theWALLSTENT stent, which is sold by Medivent-Schneider. This configurationis also well suited for practicing the present invention. To be used asthe RF coupling coil 30B, the wires forming the body or wall of thestent 106A must be electrically insulated from the surrounding tissue ofthe blood vessel 107 and must be insulated from each other where theycross except at any node wherein the helical turns are linked to formone or more sets of coupled turns. The wire used for this configurationcan be either round or flat.

An embodiment of a RF coupling coil 30C comprising a stent 106B is shownin FIG. 9 to illustrate the configuration discussed above. The RFcoupling coil 30C comprises a woven mesh 132 fabricated from insulatedwire so that overlapping segments of the woven mesh 132 do notelectrically connect in the center of the stent 106B. At each end of theRF coupling coil 30C, the wires comprising the woven mesh 132 areelectrically coupled together at nodes 134, producing the RF couplingcoil 30C. The nodes 134 are insulated from contact with body fluids orother conductors.

The couplings at the nodes 134 are preferably not made randomly or in ahaphazard fashion between the various wires comprising the woven mesh132. A first wire comprising a helical coil having, e.g., a firstconfiguration (which may be called a “right hand spiral” or RHS) has afirst end coupled to a first end of a second wire comprising a helicalcoil having a second configuration (“left hand spiral” or LHS; i.e., amirror image of the right hand spiral). The voltage induced in the twowires is equal, but opposite in sign, and the two wires are thus coupledin series and provide twice the voltage between their second ends thanthat produced between the first and second ends of either wire alone.Accordingly, the second ends of the first two wires cannot be coupledtogether at the other end of the woven mesh 132 if these two wires areto contribute to the total electrical energy derived from the woven mesh132. Rather, the wires must be “daisy chained” in series (i.e.,RHS-LHS-RHS-LHS etc.) to provide one embodiment of the RF coupling coil30C. Alternatively, a first group of wires all having the right handspiral may all be coupled in parallel (i.e., have the ends at a firstend of the woven mesh 132 coupled together, and the ends at a second endof the woven mesh 132 coupled together), with wires having the left handspiral being similarly treated but in a second group. The groups thenmay be combined in series or in parallel, or subsets of the wires may begrouped and combined.

When each wire comprising the woven mesh 132 passes around the centralaxis of the stent 106B through m degrees, and if there are a total of nsuch wires, then the equivalent number of turns in the RF coupling coil30C is equal to n×m÷360. Leads 136 and 138 convey signals to and fromthe nodes 134, coupling the woven mesh 132 to the implantable electroniccircuit 110, which may comprise any of the implantable electroniccircuits of FIGS. 1 through 6.

The woven mesh structure of the implantable RF coupling coil 30C isoften used for stents. However, it should be noted that currentlyavailable woven mesh stents are not woven from insulated wire, nor arethe nodes of the mesh at each end electrically connected in commerciallyavailable stents. In the WALLSTENT stent by Medivent-Schneider, the endsare instead free floating. It is also contemplated that an insulatedelectrical conductor could be woven into the structure of a commerciallyavailable mesh stent. Alternatively, the RF coupling coil 30C could befabricated from a woven mesh or from a plurality of spiral turns of aconductor and then the mechanical characteristics required of the stentcould be achieved by providing an interwoven wire within the RF couplingcoil 30C. It is also noted that different implantable electroniccircuits can be coupled to separate portions of the woven mesh 132comprising the RF coupling coil 30C so that the different portions ofthe RF coupling coil 30C and the implantable electronic circuits areelectrically isolated from each other, or as a further alternative, thesections can be coupled in series.

In FIG. 10, a RF coupling coil 30D in a stent 106C is illustrated thatcomprises a plurality of generally saddle-shaped coils 114 disposedwithin (or comprising) the wall of the stent 106C. Again, the RFcoupling coil 30D is coupled to the implantable electronic circuit 110.Although only a single layer of saddle-shaped coils 114 is illustrated,it is contemplated that a plurality of such interconnected layers couldbe provided for the stent 106C.

For use in electromagnetically coupling with the RF coupling coil 30D toenergize the implantable electronic circuit 110 and to provide signalsto and receive data from the transducers 44-46 (not separately shown) onthe stent 106C, an external coil 90B is provided that includes aplurality of coils 92B wrapped around a central portion of a generallyE-shaped core 94B. Lines of electromagnetic flux 112 are thus producedbetween the central leg and each of the end legs of the core 94B. Itwill therefore be apparent that this embodiment of the RF coupling coil30D and of the external coil 90B achieves optimum coupling when thedistance separating the two is minimal. Therefore, the RF coupling coil30D and the external coil 90B are best used in applications where thestent 106C is disposed relatively close to the dermal layer 102 so thattissue 104 separating the stent 106C from the external coil 90B is onlya few centimeters thick. Maximal coupling is achieved when the centralaxis of the external coil 90B is aligned with the central axis of thecoil mounted on the stent 106C.

FIG. 1A illustrates an embodiment of a RF coupling coil 121 that ishelically coiled around the circumference of a stent fabricated byslotting a metal tube 116. The insulated conductor comprising the RFcoupling coil 121 is kinked (or fan-folded) when wound around the metaltube 116 to accommodate expansion of the metal tube 116 once implantedin a blood vessel. The insulation on the RF coupling coil 121 preventsthe turns from electrically shorting by contact with the metal tube 116or with surrounding tissue. Although not shown, the RF coupling coil 121will likely be adhesively attached to the metal tube 116 at severalspaced-apart locations. The ends of the RF coupling coil 121 are coupledto one or more transducers or sensors 44-46 (not shown) through animplantable electronic circuit (also not shown) comprising any of theimplantable electronic circuits shown in FIGS. 1 through 6.

The metal tube 116 includes a plurality of generally longitudinallyextending slots 117 at spaced-apart locations around the circumferenceof the stent. These slots 117 provide the expansibility and flexibilityrequired of the stent. This design is similar to the Palmaz-Schatz stentmade by Johnson & Johnson Corporation. To avoid providing a shorted turnwith the body of the metal tube 116, the generally conventional designof the stent is modified to include a break 118 extending along theentire length of the metal tube 116. The edges of the metal tube 116 arecoupled at several joints 119 along the break 118 using a non-conductivematerial.

Metal-to-ceramic (or metal-to-glass) welded joints 119 are commonlyemployed in medical implants and other electrical devices. To minimizethermal stress in the joint 119, the metal and the glass or ceramic musthave similar thermal expansion coefficients. For example, KOVAR™ alloy,a nickel-iron alloy (29% Ni, 17% Co, 0.3% Mn and the balance Fe) is onematerial that can be used to form glass to metal seals that can bethermally cycled without damage. This material can be used to formportions of the metal tube 116 disposed along the break 118. Glass orceramic bonds comprising the joints 119 then will not experience muchthermal stress when the temperature of the stent changes. This materialis commonly used in lids that are bonded onto ceramic chip carriers inthe integrated circuit industry and thus is readily available.

An alternative design for a stent formed from a non-woven wire 145 aboutwhich the RF coupling coil 121 is coiled is illustrated in FIG. 11B. TheRF coupling coil 121 is again formed of an insulated conductor that ishelically coiled about the circumference of the stent. The body of thestent comprises a plurality of zigzag shapes formed of wire 145 that arejoined by non-conductive (i.e., glass or ceramic) joints 146 atspaced-apart points that prevent the wires 145 from forming any shortedturns. This stent configuration is similar to that of the ACS RXMULTI-LINK stent made by Medtronic and the GFX (AVE) stent produced byArterial Vascular Engineering.

In those cases where stents are implanted relatively deeply inside thepatient's body, at some distance from the surface of the patient's skin,an alternative external coil 154 can be employed, generally as shown inFIG. 12. In this example, a stent 144 comprising the RF coupling coil30C (FIG. 9) is implanted within an artery 152, which is disposed withina thigh 150 of the patient. Alternatively, the stent 144 may beimplanted, for example, in the descending aorta, the iliac arteries orto provide therapy to a tumor that is deeply within the abdomen. Tocouple with the RF coupling coil 30C, the external coil 154 includes aplurality of turns 156 sufficient in diameter to encompass the thigh150. A RF shield 160 encloses the outer extent of the external coil 154,so the external coil 154 is insensitive to capacitively coupled noise. Alead 158 couples the external coil 154 to a power supply and monitoringconsole 101. The external coil 154 can be made sufficiently large toencompass the portion of the body in which the implanted stent 144 isdisposed such as the torso, a limb of the patient, or the neck of thepatient. Coupling is maximized between the external coil 154 and the RFcoupling coil 30C (or other RF coupling coil) used on the stent 144 whenthe central axes of both the RF coupling coil 30C and the external coil154 are coaxially aligned and when the implanted stent 144 is generallynear the center of the external coil 154. Coupling between the RFcoupling coil 30C and the external coil 154 decreases with increasingseparation and begins to degrade significantly when the implanted stent144 is more than one external coil 154 radius away from the center pointof the external coil 154. In addition, coupling is minimized when thecentral axis of the external coil 154 is perpendicular to the axis ofthe RF coupling coil 30C.

Description of the Diagnostic Applications of Transducers

An ultrasonic transducer for monitoring flow or fluid velocity through astent should be relatively compact and included in or mounted on thewall of a stent. Typical prior art ultrasonic transducers include aplanar slab of a piezoelectric material having conductive electrodesdisposed on opposite sides thereof. Since such elements are planar, theydo not conform to the circular cross-sectional shape of a stent.Moreover, prior art transducers are not compatible for use with a stentthat is implanted within a patient's body and which is intended to beleft in place for an extended period of time. Also, it is apparent thatconventional ultrasonic transducer elements will not readily yield tobeing deformed into a compact state for implacement within a bloodvessel, followed by expansion of a stent body to apply radiallyoutwardly directed force to compress the deposits within a blood vessel.

FIGS. 13 through 15 show an embodiment of an extremely low profileultrasonic transducer comprising conformal transducer arrays 174A and174B, which are disposed on opposite sides of a stent 168. While theconformal transducer arrays 174A and 174B are described in conjunctionwith their application as diagnostic transducers, the conformaltransducer arrays 174A and 174B are also useful as therapeutictransducers. Since it is contemplated that this type of ultrasonictransducer assembly might be used on several different designs ofstents, details of the stent 168 are not illustrated. Instead, only aportion of its outline 170 is shown. Ideally, each conformal transducerarray 174A and 174B comprises a piezoelectric plastic used as atransduction material and having sufficient flexibility to allow thetransducer elements to conform to the circular cross section of the wallof the stent 168 when the stent 168 is inserted through the patient'svascular system and to flex as the stent 168 is expanded within a bloodvessel.

When used for transit time measurements, as shown in FIGS. 13 and 14,the conformal transducer arrays 174A and 174B are disposed generally onopposite sides of the stent 168 and encompass much of the innercircumference of the stent 168. However, when a pulsed Dopplermeasurement is made using the conformal array transducer 174A, only asingle such conformal array transducer 174A is required, since theconformal array transducer 174A first produces an ultrasonic wave thatis transmitted into the lumen of the stent 168 and then receives an echoreflected back from the fluid flowing through the stent 168. If used forcontinuous wave (CW) Doppler measurements, the pair of conformaltransducer arrays 174A and 174B disposed on opposite sides of the stent168 are again needed, one conformal transducer array 174A or 174Bserving as a transmitter and the other as a receiver. In each case, itis presumed that the fluid has a non-zero flow velocity componentdirected along an ultrasonic beam axis of the ultrasonic wave producedby the conformal transducer array 174A or 174B serving as a transmitter.

The conformal transducer arrays 174A and 174B shown in FIGS. 13 through15 produce ultrasonic beams 178 that are tilted relative to thetransverse direction across the stent 168 in substantially equal butopposite angles with respect to the longitudinal axis of the stent 168.Since dual beam transit time measurements are implemented by theconformal transducer arrays 174A and 174B, the results areself-compensating for tilt angle errors. This form of self-compensationis only required where the alignment of the conformal transducer arrays174A and 174B relative to the longitudinal axis of the stent 168 may beimperfect. For transit time measurements made on stents 168 wherein thealignment of the conformal transducer arrays 174A and 174B relative tothe longitudinal axis of the stent 168 remains accurately known, anopposed pair of conformal transducer arrays 174A and 174B disposed onopposite sides of the stent 168 is sufficient so that the addedcomplexity of the dual beam transducer geometry is not required for selfcompensation.

In the case of pulsed Doppler velocity measurements, a single conformaltransducer array 174A would again likely be adequate so long as thealignment of the conformal transducer array 174A to the stent 168 isaccurately controlled. If the alignment of the conformal arraytransducer 174A is not controlled or not well known, a second suchconformal transducer array 174B can be used to gather velocity dataalong a second beam axis using pulsed Doppler velocity measurements.Assuming that the second axis is tilted in an equal but oppositedirection as the first axis, the Doppler measurements made by the twoconformal transducer arrays 174A and 174B should be self-compensatingfor tilt errors. In this case, the second conformal transducer array174B could be mounted on the same or on an opposite side of the stentfrom that where the first conformal transducer array 174A is mounted toimplement the Doppler measurements.

For CW or pseudo-CW Doppler velocity measurements (in which a relativelylong duration pulse of ultrasonic waves is produced), the transit signalis applied for a sufficiently long period so that a second conformaltransducer array 174B is needed to receive the echo signals. In thiscase, a single set of diametrically opposed conformal transducer arrays174A and 174B can be used.

As perhaps best illustrated in FIG. 14, the conformal transducer arrays174A and 174B need not wrap entirely around the stent 168. In theillustrated embodiment, the conformal transducer arrays 174A and 174Beach span an arc of approximately 60° around the longitudinal axis ofthe stent 168 (i.e., about the center of the circular stent 168 as shownin FIG. 14). This geometry produces a measurement zone through whichultrasonic beams 178 propagate that is nominally equal to about 50% ofthe outer diameter of the stent 168. If used for Doppler velocitymeasurements, it is contemplated that the conformal transducer array174A need cover only a central portion of the stent 168. As a result,the span of the conformal transducer arrays 174A and 174B can be reducedfrom about 60° to about 45°.

To produce a wide, uniform ultrasonic beam such as that needed fortransit time measurements of flow, the conformal transducer arrays 174Aand 174B must produce ultrasonic waves having a wave front characterizedby a substantially uniform amplitude and phase. As shown in FIG. 13,lateral projections through each of a plurality of transducer elementscomprising the conformal transducer arrays 174A and 174B are indicatedby straight lines 176. These straight lines 176 indicate the centers ofthe transducer elements and are perpendicular to the axis of propagationof waves 178 (represented by bi-directional arrows directed along theaxes of propagation of the ultrasonic waves). In one embodiment, thespacing between the element centers, i.e., between the straight lines176, is approximately equal to a phase angle of 90° at the excitationfrequency of the conformal transducer arrays 174A and 174B. Thus,starting at the top of FIG. 13 and working downwardly, transducerelements disposed along each of the displayed straight lines 176 produceacoustic waves that are successively delayed by 90°, or one-quarterwavelength in the fluid medium through which the ultrasonic wavespropagate. For tissue, a sound velocity of 1,540 meters/second isnormally assumed, so that the physical spacing of the projected straightlines would typically be defined by the following:Projected Spacing in millimeters=1.54/(4*F ₀),where F₀ is equal to the center frequency in MHz. If zero degrees isassigned to the top-most element of the conformal transducer array 174A,the next element would operate at −90° relative to the top element,followed by an element operating at −180°, and then one operating at−270°, and finally by an element operating at 0° relative to the topelectrode. Thus, the conformal transducer array 174A produces asuccession of ultrasonic waves spaced apart by a 90° phase shift,thereby achieving a desired phase uniformity across the conformaltransducer array 174A.

While the discussion herein is in terms of phase shifts of 900, it willbe appreciated that other types of transducer element spacings orrelative displacements may require different phase shifts. For example,three phase transducers are known that employ a phase shift of 120°between adjacent elements. Additionally, physical displacements of thetransducer elements in the direction of propagation of the acousticwaves may require different or additional phase shifts between theelectrical signals coupled to the elements. It is possible to phaseshift these signals to provide a uniform phase front in the propagatingacoustic wave using conventional techniques.

Amplitude uniformity can be achieved in the ultrasonic wave front byapodization or “shaving” of the elements of the conformal transducerarrays 174A and 174B. Although shaving could be achieved in a variety ofways, one embodiment controls shaving by varying the area of eachelement.

In one embodiment, the conformal transducer arrays 174A and 174B arecarried on a band 172 made from the piezoelectric plastic material usedfor the element substrate, which is sized to fit snugly around an outersurface of the stent 168 or inserted into the lumen of the stent 168 (asshown in FIG. 14). The band 172 is intended to position the conformaltransducer arrays 174A and 174B in acoustic contact with the wall ofstent 168, when the band 172 is wrapped around the stent 168, or tomaintain the conformal transducer arrays 174A and 174B against the innersurface of the stent 168, when the band 172 is inserted into the lumenof the stent 168. Contact of the band 172 around the outer surface ofthe stent 168 assures that the ultrasonic waves produced by the elementsof the conformal transducer arrays 174A and 174B are conveyed into thefluid flowing through the interior of the lumen. In one embodiment, thepiezoelectric plastic comprising the band 172 is fabricated from amaterial such as polyvinylidene fluoride (PVDF), poly(vinylcyanide-vinyl acetate) copolymer (P(VCN/VAc), or poly(vinylidenefluoride-trifluoroethylene) copolymer (P(VDF-TrFE)), available from AMPSensors of Valley Forge, Pa. In one embodiment, P(VDF-TrFE) is usedbecause of its high piezoelectric coupling and relatively low losses.

Referring now to FIG. 15, further details of the conformal transducerarrays 174A and 174B are illustrated. In this embodiment, adjacentelements of the conformal transducer arrays 174A and 174B produceultrasonic waves differing by 90°. In the view shown in FIG. 15, a cutline 175 intersects the lateral center of the conformal transducer array174B. In practice, any cut would more likely extend through the band 172at a point approximately midway between the conformal transducer array174A and the conformal transducer array 174B. Electrodes comprising eachelement of the conformal transducer arrays 174A and 174B can bephotolithographically generated on the piezoelectric plastic substratecomprising the band 172. Alternatively, the elements can be formed on anon-piezoelectric material comprising the band 172, and then thematerial with the elements formed thereon can be bonded to apiezoelectric substrate in each area where a conformal array transducerelement is disposed. In this latter embodiment, it is contemplated thata flexible circuit material such as a polyimide could be employed forthe band 172 and that conventional photolithographic processing methodsmight be used to fabricate the conformal array transducer circuitry onthe band 172. Further, the centers of alternating conformal arrayelements are coupled together electrically via conductors 180 (shown asdashed lines) in FIG. 15. Not shown in FIGS. 13 through 15 are the leadsthat extend from an implantable electronic circuit used to drive theconformal transducer arrays 174A and 174B. Any of the implantableelectronic circuits shown in FIGS. 1 through 6 could be used for theimplantable electronic circuits.

The pattern of elements comprising each of the conformal transducerarrays 174A and 174B and the boundary of each conformal transducer array174A and 174B (top and bottom as shown in FIG. 15), define sinusoidalsegments. The period of the sine wave from which these sinusoidalsegments are derived is approximately equal to the circumference of theband 172. Further, the amplitude of that sine wave generally depends onthe desired beam angle relative to the longitudinal axis of the stent.For the sinusoidal segment employed for each electrode, the amplitude isdefined by:Amplitude=D*tan Θ.

Similarly, the amplitude of the sinusoidal segment defining the boundaryof each conformal array 174A and 174B is defined by:Amplitude=D/(tan Θ)),where Θ is equal to the angle between the longitudinal axis of the stent168 (see FIG. 13) and the ultrasound beam axis 178 and D is equal to theexternal diameter of the stent 168. Accordingly, it should be apparentthat one sinusoidal template could be used to draw all of the transducerelements and a second sinusoidal template (differing only in amplitudefrom the first) could be used to draw the boundary of each conformalarray transducer 174A and 174B. The transducer elements are displaced orspaced apart from one another as required to achieve the phaserelationship described above in connection with FIG. 13. In addition,the actual physical electrode pattern and placement of the elements onthe band 172 can be determined by finding intersection loci between theband 172 as wrapped around (or within the inner circumference of) thestent 168 and equally-spaced planes. The spacing between these planes isdefined by the equation noted above for the projected spacing.

The conductors 180 that couple to adjacent transducer elements differ inphase by 90°. There are two ways to achieve the 90° phase variationbetween the ultrasonic waves produced by successive electrodes in theconformal transducer arrays 174A and 174B. In the first approach, auniformly polarized piezoelectric plastic substrate is used and everyfourth element is coupled together, producing four groups of elements orelectrodes that produce ultrasonic waves having phase relationships of0°, 90°, 180° and 270°, respectively. Alternatively, a zone polarizedpiezoelectric plastic substrate could be used and every other elementcan be coupled together (as shown in FIG. 15). Each of these two groupsis then coupled to provide an in phase and a quadrature phasetransceiving system, so that ultrasonic waves are produced by adjacentelements in each group have a relative phase relationship of 0° and 90°.In the first approach, a multi-layer interconnect pattern is required tocouple to all traces for each of the transducer elements in the fourgroups. In addition, a more complex four-phase electronic driving systemthat includes a phase shifter is required. Specifically, the signalapplied to each of the four groups must differ by 90° between successiveelements to achieve the 0°, 90°, 180° and 270° driving signals. Thephase shifter, e.g., may be included in the modulator that drives theconformal transducer arrays 174A and 174B (which may be included as apart of the RF decode section 40 of FIGS. 1 through 3 or the RFdecode/control section 66 of FIGS. 4 through 6), and provides the phaseshifted excitation signals applied to each successive element of theconformal transducer arrays 174A and 174B.

In the second approach, which may be preferred in some embodimentsbecause it may simplify the electronic package required and because itmay facilitate use of a simpler, double-sided electrode pattern, thepiezoelectric plastic material must be locally poled in a specificdirection, depending upon the desired phase of the electrode at thatlocation. A poling direction reversal provides a 180° phase shift,eliminating the need for 180° and 270° phase-shifted signals. Thus, thezones of the substrate designated as 0° and 90° would be connected tothe in-phase and quadrature signal sources with the elements poled inone direction, while zones for elements designated to provide a relativephase shift of 180° and 270° would be connected to the in-phase andquadrature signal sources with the elements poled in the oppositedirection. The elements producing ultrasonic waves with a relative phaserelationship of 0° and 180° would comprise one group (e.g., in-phase)and the elements producing ultrasonic waves with a relative phaserelationship of 90° and 270° would comprise a second group (e.g.,quadrature). Poling the different groups of elements in local regions inopposite directions is achieved by heating the material above the Curietemperature, applying electric fields of the desired polarities to eachof those areas and then cooling the material below the Curie temperaturewhile maintaining the electric fields. This occurs during manufacture ofthe conformal transducer arrays 174A and 174B. The final element wiringpattern required to actually energize the conformal transducer arrays174A and 174B when they are employed for monitoring flow and/or velocityof fluid through the vessel 170 would preclude applying electric fieldsin opposite polarity. Accordingly, the required poling relationshipwould have to be performed using either temporary electrodes or byproviding temporary breaks in the actual electrode pattern employed inthe final conformal transducer arrays 174A and 174B.

In one embodiment, to achieve a desired frequency of operation, it iscontemplated that the electrode mass would be increased to a point wellbeyond that required for making electrical connections. This added masswould act together with the piezoelectric plastic material to form aphysically resonant system at a desired frequency. In this manner, arelatively thinner and more flexible piezoelectric plastic material canbe used for the substrate comprising the band 172. Use of mass loadingis conventional in the art of ultrasonic transducer design.

While the fluids within the vessel 170 may provide an effective groundplane, in one embodiment, a conductive layer 177 (see FIG. 14) isincluded. The conductive layer 177 may be disposed on the inside of theband 172 as illustrated (between the conformal array transducer 174A andthe band 172). In one embodiment, the conformal array transducer 174Acomprises a sandwich of two layers of piezoelectric plastic, with thedriven electrodes disposed between the two layers of piezoelectricplastic, and ground planes disposed to either outside surface of theconformal array transducer 174A. The transducer then comprises a groundplane, a layer of piezoelectric plastic, a layer of driven electrodes, alayer of piezoelectric plastic and the other ground plane. Thisembodiment has the advantage that the conformal array transducer 174A iswell shielded and further is electrically isolated from body fluids.Other arrangements will also be apparent to those of skill in the art.When the conformal transducer arrays 174A and 174B are used to transmitultrasonic waves, the conductive layer 177 may be floating (a “virtualground”) or may be coupled to a ground or common circuit (e.g., 34,FIGS. 1 through 6). When the conformal transducer arrays 174A and 174Bare used to receive ultrasonic waves, the conductive layer 177 should becoupled to a common circuit or ground to reduce noise and EMI.

In FIGS. 16A and 16B, an alternative approach for monitoring thevelocity of a fluid through an interior 250 of a stent 240 isillustrated. A pair of ultrasonic transducers 242A and 242B may berealized as conformal transducer arrays, e.g., as described inconjunction with FIGS. 13 through 15, or may be realized in other forms,and may find application as therapeutic transducers in addition to beinguseful as diagnostic transducers.

In the embodiment illustrated in FIGS. 16A and 16B, the pair ofultrasonic transducers 242A and 242B are mounted in relatively closeproximity within a wall 244 of the stent 240. Alternatively, theultrasonic transducers 242A and 242B may be disposed externally incontact with the outer surface of a stent (not shown). The ultrasonictransducers 242A and 242B each produce a pulse and receive an echo backfrom fluid flowing through the interior 250 of the stent 240, the echoesbeing scattered from the fluid flowing therein. In this embodiment, thesignal received from the ultrasonic transducer 242A in response to theecho is correlated with a similar signal from the ultrasonic transducer242B, resulting in a time delay estimate. The velocity of the fluid isthen computed by dividing a distance between the center of theultrasonic transducer 242A and the center of the ultrasonic transducer242B by the time delay that was determined from the correlationanalysis. This is explained in more detail as follows.

The interaction of the blood with the ultrasound, even when it is movingat constant velocity, gives rise to a moving acoustic “speckle” pattern.The term speckle, as used herein, has a similar meaning in ultrasonicsas in optics. It results any time that narrow-band illumination is used.Optical speckle is visible when a laser (e.g., a pointer) illuminates aplain white wall. When illuminated with wideband illumination, the wallappears white and smooth. When illuminated with laser light, the wallappears to have bright and dark spots, hence the term speckle. Acousticspeckle is visible in medical ultrasound images, when the system is usedto image homogeneous soft tissues such as the liver. As in optics, theacoustic speckle pattern is stationary and constant unless the tisse orflood is moving with respect to the imaging system. The same phenomenonis exploited in Doppler systems. When the echo return from moving bloodis constant, there is no observable Doppler shift in the echo signal.

The blood consists of thousands of scatterers, and the ultrasoundreflects from ensembles of these scatterers. The amplitude and phase ofthe echo, at a given range, depends on the local distribution ofscatterers, which is random. The random signal of echo amplitude andphase at a given depth repeats as the blood flows past the secondultrasonic transducer 242B, if the spacing between the two ultrasonictransducers 242A and 242B is such that the ensembles of scatterers havenot changed significantly, i.e., if the two ultrasonic transducers 242Aand 242B are close enough to each other that turbulence has notsignificantly disrupted the ensembles of scatterers. Correlation ofnominally identical random patterns that are displaced in time by anamount equal to the time required for the blood to move from the firstbeam to the second one allows the velocity to be determined when theseparation between the two ultrasonic transducers 242A and 242B isknown.

In other words, the first ultrasonic transducer 242A receives an echosignal that provides a speckle “image”—where the distance from theultrasonic transducer 242A is along the vertical dimension in FIGS. 16Aand 16B, and the successive echo returns are along the horizontaldimension. The two “images” from the two ultrasonic transducers 242A and242B are correlated in the horizontal dimension, and what results is aninstantaneous map of travel time vs. depth.

The sampling aperture for this system is much shorter than the timerequired for a heartbeat. Accordingly, a series of measurements, whichmay be taken during the interval between two successive heartbeats, maybe processed or compared to determine peak, minimum and average bloodvelocity when these data are desired.

Unlike a Doppler system, the echoes in a correlation type transducersystem like that shown in FIGS. 16A and 16B are not frequency shifted.Instead, the velocity signal is extracted by correlating the echoamplitude versus time signals for a pair of range bins. The velocityversus time is independently determined for each range bin, resulting ina time dependent velocity profile across the diameter of the stent 240.

The conformal transducer arrays 174A and 174B of FIGS. 13 through 15 canbe formed on the band 172, but alternatively, can be included within thestructure of a stent, i.e., within its wall. FIG. 17 illustrates aportion of a cross-sectional view of the conformal array transducer 174Aof FIGS. 13 through 15 fabricated in a stent wall 190. The entireconformal array transducer 174A is fitted within the stent wall 190.Details of the stent wall 190 are not illustrated, since it iscontemplated that many different types of stent configurations aresuitable for carrying the conformal transducer arrays 174A and 174B. Thestent wall 190 is shown inside a blood vessel wall 204. A biocompatibleouter coating 192 comprises the next layer, protecting the conformaltransducer arrays 174A and 174B from contact with bodily fluids. In oneembodiment, the outer coating 192 comprises PARYLENE™ material,available from Specialty Coating Systems of Indianapolis, Ind. Outercoatings 192 comprising PARYLENE™ material may be grown to a desiredthickness via vapor coating. In one embodiment, the outer coating 192 isgrown to a thickness of between 0.0001″ to 0.0002″ (2.5 to 5 microns).Below the outer coating 192 is an acoustic backing 194 comprising aconventional, or a syntactic foam, i.e., a polymer loaded with hollowmicrospheres, that serves both for acoustic isolation and dampening andto minimize capacitive loading.

In one embodiment, the acoustic backing 194 comprises one volume ofEPOTEK 377 or 301-2 epoxy glue available from Epoxy Technology ofBillerica, Mass. mixed, e.g., with two or more volumes of microballoonsavailable from PQ Corp. of Parsippany, N.J. Microbubbles such as PM6545acrylic balloons having an average diameter of 100 microns are employedin one embodiment, with the acoustic backing being 10 to 20microballoons thick (one to two mm). The acoustic backing 194 has arelatively low dielectric constant (e.g., <10), thereby minimizingcapacitive loading between the electrodes and surrounding tissue. Theacoustic backing 194 thus insulates the transducer elements from thesurrounding fluid and tissue in a capacitive sense and also in anacoustic sense. The next layer comprises a rear electrode 196. A frontelectrode 200 is spaced apart from the rear electrode by a piezoelectricplastic layer 198. In one embodiment, the front electrode 200 is alsothe conductive layer 177 of FIG. 14. As noted above, in the embodimentillustrated in FIGS. 13 through 15, the piezoelectric plastic layer 198of FIG. 17 comprises the band 172 of FIGS. 13 through 15. Thepiezoelectric layer 198 (or the band 172) has a relatively lowdielectric constant, e.g., from about six to eight, compared to tissue(approximately 80).

In one embodiment, the rear electrode 196 and the front electrode 200comprise multi-layer structures (although separate layers are notshown). For example, the electrodes 196 and 200 will include a metalliclayer that bonds well to the piezoelectric plastic layer 198, forexample, titanium, followed by a highly conductive layer, for example,copper, followed by an oxidation resistant layer, for example, gold, andincludes other metallic barrier layers, where appropriate, to preventreaction between these layers. Such multi-layer systems are conventionaland are suited for use as the electrodes 196 and 200 in the conformaltransducer arrays 174A and 174B.

In one embodiment, the front electrode 200 is the “common electrode” forthe transducer elements and serves as a RF shield. A front coating 202serves as an acoustic coupling between the conformal transducer arrays174A and 174B and the fluid in the lumen of the stent. In addition, thefront coating layer 202 serves as a biocompatible layer, providing abarrier to fluid ingress into the conformal array transducers 174A and174B.

In both the conformal array transducers 174A and 174B provided in theband 172 (as shown in FIGS. 13 through 15) and the conformal arraytransducer 174A included within the structure of the stent wall 190, asillustrated in FIG. 17, it is contemplated that adhesive layers (notshown) may be used between the various layers. However, certain layerssuch as the front and rear electrodes 200 and 196 will likely need notbe adhesively coupled to the piezoelectric layer 198 ifphotolithographically formed on the piezoelectric layer 198. Otherlayers may not require an adhesive to couple to adjacent layers, e.g.,if formed of a thermoset material that self bonds to an adjacent layerwhen set.

As noted above, one of the advantages of the conformal transducer arrays174A and 174B is a relatively low profile. In some cases, a stent mayintegrally accommodate a relatively thicker profile transducer assembly.An embodiment of a tilted element transducer 210 coupled to a stent 203that is useful as a diagnostic transducer or as a therapeutic transduceris illustrated in FIG. 18. Each element comprising the tilted elementtransducer 210 includes the rear electrode 196 and the front electrode200 disposed on opposite sides of the piezoelectric material 198.Conventional prior art transducers for producing an ultrasonic waves usea single such element that has a substantially greater width that isoften too great for inclusion within a stent assembly. In contrast, thetilted element transducer 210 includes a plurality of elements likethose shown in FIG. 18 that minimize the radial height (or thickness) ofthe tilted element transducer 210.

An outer coating 195 again serves the function of providing abiocompatible layer to protect the transducer components containedtherein from exposure to bodily fluids. When the outer coating 195comprises PARYLENE alone, an RF shield 193 extends over the tiltedelements, immediately inside the outer coating 195. When the outercoating 195 comprises a container (as illustrated), it includes an outercoating of a material such as PARYLENE. When the outer coating 195comprises a conductive material, a separate RF shield such as the RFshield 193 may not be required. The acoustic backing 194 is disposedbelow the RF shield 193 or the outer coating 195.

An acoustic filler material 212 is disposed between the front electrode200 and the front coating 202, on the interior surface of the stent 203,and is used to fill in the cavities in front of the transducer elements.The acoustic filler material 212 is characterized by a relatively lowultrasonic attenuation, so that it readily conveys the ultrasonic wavesproduced by the transducer elements into the lumen of the stent 203. Inone embodiment, in order to minimize reverberations of the ultrasonicwaves in this acoustic filler material 212, its acoustic impedance,which is related to sound velocity times density, is approximately equalto that of the fluid in the vessel. The velocity of sound in theacoustic filler material 212 should also be close to that of the fluidflowing through the stent 203 so that the sound beam is notsignificantly deflected by the acoustic filler material 212. In anotherembodiment, the acoustic filler material 212 has a relatively low soundvelocity compared to the fluid. In this embodiment, the acoustic fillermaterial 212 acts as an acoustic lens that deflects the sound beingproduced by the elements of the tilted element transducer 210. Forexample, materials such as silicones or fluorosilicones typically havingsound velocities about 1000 meters per second (compared to a soundvelocity of approximately 1540 meters per second for blood) may be used.Low velocity lenses are conventional. A benefit of using a low velocityacoustic filler material 212 is that the elements of the tilted elementtransducer 210 can be tilted about 30% less than would be requiredotherwise. As a result, the overall height of the tilted elementtransducer 210 portion of the stent 203 can be made about 30% thinnerthan would be possible without the low velocity acoustic filler material212. In combination, the plurality of tilted elements of the tiltedelement transducer 210 produce an ultrasonic wave 214 that propagates atan angle relative to the longitudinal axis of the stent, which isrepresented by a center line 216 in FIG. 18.

FIG. 19A is an isometric view of an implantable integrated circuit (IC)transducer 220 mounted on a tubular stent 222, which may comprise astent similar to that described in conjunction with FIG. 11A above.Wires form a RF coupling coil 223 coupled to the implantable IC sensor220 via wires 225. The wires comprising the RF coupling coil 223 areformed in a zigzag shape to allow for expansion of the tubular stent 222when it is installed. The implantable IC sensor 220 may includediagnostic or therapeutic transducers. In one embodiment, the sensingapparatus of the implantable IC sensor 220 faces the interior of thetubular stent 222, as is described more fully with respect to FIG. 19Bbelow.

FIG. 19B illustrates the implantable IC sensor 220 mounted on thetubular stent 222, so that the implantable IC sensor 220 overlies asensor window opening 224 in the tubular stent 222. Conductive adhesiveor solder 228 couples the implantable IC sensor 220 contacts to thetubular stent 222 (or to conductors that are coupled to one of theimplantable electronic circuits shown in FIGS. 1 through 6). Abiocompatible coating 226 (analogous to the biocompatible coating 192 ofFIG. 17) encloses the implantable IC sensor 220, except in the area ofthe sensor window opening 224 through which the implantable IC sensor220 is in contact with the fluid flowing through the lumen of thetubular stent 222. The portion of the tubular stent 222 on which theimplantable IC transducer 220 is mounted may be made rigid, e.g., bythickening it, to prevent damage to the implantable IC transducer 220during the installation of the tubular stent 222. Optionally, a circuitboard (not illustrated in FIG. 19B) may be included between theimplantable IC transducer 220 and the tubular stent 222 to facilitatemaking electrical interconnections to the RF coupling coil 223.

FIG. 19C illustrates an embodiment wherein the implantable IC transducer220 is coupled to a woven mesh stent 222A. The woven mesh stent 222Acomprises wires woven to form a mesh comprising a RF coupling coil 223Aas described in conjunction with FIGS. 8 and 9 above. Wires 225A couplethe RF coupling coil 223A to the implantable IC transducer 220. Theimplantable IC sensor 220 may include diagnostic transducers, and thewoven mesh stent 222A may include therapeutic transducers (notillustrated). In one embodiment, the sensing apparatus of theimplantable IC transducer 220 is held in place via an encapsulant 226Ato face the interior of the woven mesh stent 222A, as is described morefully with respect to FIG. 19D below.

FIG. 19D is an enlarged partial cross-sectional side view of theimplantable IC transducer 220 mounted on the woven mesh stent 222A ofFIG. 19C. The implantable IC transducer 220 is coupled to the wirescomprising the body of the woven mesh stent 222A by the encapsulant 226Awhich may also serve as a biocompatible fluid barrier and as aninsulator. This keeps the implantable IC transducer 220 from contactingbody fluids except at the sensing interface which is mounted within anopening 224A in the wall of the woven mesh stent 222A. A flexiblecircuit substrate 227 optionally is employed to provide mechanicalattachment and electrical coupling to the implantable IC transducer 220via solder bumps 228 or other conductive and mechanically robustinterconnection. In the embodiments of FIGS. 19A through 19D, theimplantable IC transducer 220 may comprise the implantable electroniccircuits of any of FIGS. 1 through 6 and the stents 222 and 222A mayalso include other transducers such as diagnostic or therapeutictransducers.

It is contemplated that the implantable IC transducer 220 might be usedfor measuring parameters such as pressure, temperature, blood gasconcentration and insulin level or the levels of other metabolite suchas glucose or sodium in the blood stream of a patient in which a stentthat includes the IC sensor 220 is implanted. As explained above, theimplantable IC sensor 220 is electrically energized with electricalpower that is electromagnetically coupled to the RF coupling coil 223Athat comprises the stent body 222A or which is incorporated as one ormore separate insulated windings within the stent wall structure.Signals produced by the IC sensor 220 are converted to data signals,which are electromagnetically coupled to a monitor outside the patient'sbody, also as explained above. In certain applications of implantable ICsensors 220, it may be advantageous to perform a differentialmeasurement between two spaced-apart locations on the stent body 222 or222A. Thus, to monitor fluid flow through the lumen of a stent 222 or222A, a differential pressure measurement made by transducersrespectively disposed adjacent the proximal and distal ends of the stent222 or 222A provide an indication of blood flow and of any blockage withthe lumen of the stent 222 or 222A.

If an external source of heat is applied to heat the blood or otherfluid flowing through the lumen of a stent 222 or 222A, flow can bedetermined by monitoring the temperature of the fluid with IC sensors220 that are responsive to that parameter. An external source of RFenergy electromagnetically coupled into the stent 222 or 222A, asdisclosed above, can both provide the electrical power for thecomponents of the stent transducer system and provide the power forheating the fluid. To avoid tissue damage, the maximum stent temperatureshould remain below 42.5° C., which is well established as thetemperature above which hyperthermia and irreversible tissue damageoccur. By analyzing the resultant temperature vs. time “thermal washout”curve, the flow rate of fluid through the stent 222 or 222A can bedetermined. A differential temperature measurement made by temperaturesensors disposed adjacent the opposite ends of the stent 222 or 222Acould also be used to determine flow through the stent lumen. Using thesignals from these sensors, two temperature vs. time curves can bedeveloped simultaneously. Differences in the observed thermal washoutcurves should be primarily a function of flow through the lumen and thusindicative of that parameter.

Other methods can be employed to determine flow based on temperaturemeasurements. For example, by modulating the RF power used to heat thestent 222 or 222A, the temperature vs. time curves will exhibit themodulation frequency. The temperature vs. time curves produced byspaced-apart temperature sensors can be filtered with a relativelynarrow bandwidth filter. The phases of the two filtered signals arecompared to extract a flow velocity through the stent 222 or 222A. Thesignal processing concept of this approach is conceptually similar tothat used for measuring cardiac output using a catheter-mounted heaterand temperature sensors, as disclosed in U.S. Pat. No. 5,277,191entitled Heated Catheter For Monitoring Cardiac Output.

Several types of IC sensors 220 that might be incorporated within astent in accord with the present invention are disclosed in previouslyissued U.S. patents. For example, U.S. Pat. No. 4,020,830 (andre-examination certificate B1 U.S. Pat. No. 4,020,830) entitledSelective Chemical Sensitive FET Transducers and U.S. Pat. No. 4,218,298entitled Selective Chemical Sensitive FET Transducer describe chemicalfield effect transistor (FET) transducers that are sensitive to specificchemical substances or to their properties. U.S. Pat. No. 4,935,345entitled Implantable Microelectronic Biochemical Sensor IncorporatingThin Film Thermopile discloses an implantable microelectronicbiochemical sensor that incorporates a thin film thermopile for use inmonitoring concentrations of glucose or other chemicals present in theblood stream. Various types of pressure sensing devices appropriate forincorporation in the wall of a graft are readily available from a numberof different commercial sources, including SRI Center for MedicalTechnology of Palo Alto, Calif.

Other prior art devices are potential candidates for use as IC sensors220 on stents 222 or 222A. In Evaluation of a Novel Point-of-CareSystem, the I-Stat Portable Clinical Analyzer, CLINICAL CHEMISTRY, Vol.39, No. 2, 1993, K. A. Erickson et al. describe a blood analyzer basedon disposable IC biosensors that can quantify sodium, potassium,chloride, urea, nitrogen and glucose levels. A good overview of acousticwave biosensors is provided by J. C. Andle et al. in Acoustic WaveBiosensors, published in the 1995 IEEE Ultrasonics SymposiumProceedings, IEEE cat. no. 0-7803-2940-6/95, pp. 451-460. Other types ofIC biosensors are described in the art. However, it is sufficient forthis disclosure to recognize that such IC sensors 220 are well known inthe art and are generally available or readily fabricated for use onstents 222 or 222A (or other stent designs) as described above.

In the embodiments of FIGS. 19A through 19D, the implantable sensor IC220 senses the concentration of a particular substance or anotherparameter that was determined to require monitoring prior to implantingthe implantable sensor IC 220 or that is selected from a plurality ofsensing capabilities provided on the implantable sensor IC 220 inresponse to control signals coupled via the RF coupling coil 223 or223A. This diagnostic information is then used in conjunction with thetherapeutic transducers of any of FIGS. 13 through 15, 17, 18, 20, 21and 23 through 28.

A stent may include other types of sensors beside the ultrasonictransducers and the IC sensor 220 noted above. FIG. 20 illustrates anoutline of a stent 232 that includes a strain sensor comprising strainsensing filaments 230 mounted on the stent 232. In the disclosedembodiment, strain sensing filaments 230 are wound around the stent 232to measure displacement that is converted to a signal for transmissionoutside the body by an implantable IC 220A. The filaments 230 exhibit achange in electrical resistance with strain and are therefore usable tosense the strain experienced by the stent 232 when it is expanded insidea blood vessel. It is contemplated that the strain sensing filaments 230be used only for strain sensing, so that their dimension, dispositionand metallurgy can be optimized for that function. Alternatively, thestrain sensing filaments 230 can comprise part of the structural body ofthe stent 232 so that they also provide a mechanical function related tothe conventional function of the stent 232. It is also contemplated thatstrain gauges (not separately shown) can be used instead of the strainsensing filaments 230. The strain gauges can be mounted to the stent 232at selected spaced-apart locations to measure displacement. Metallizedpolyimide substrate strain gauges are suited to this application, bywrapping the substrates around the body of the stent 232 and attachingthe substrates to the body of the stent 232 at selected spaced-apartpoints. By monitoring the size of stent 232 as it is expanded, straingauges or other strain measuring sensors can determine when a desiredexpansion of the stent 232 has been achieved. Alternatively, the straindata can be employed to assess the elasticity of the stent 232 and bloodvessel structure by monitoring the dynamic strain over cardiac cycles,i.e., with successive systolic and diastolic pressure levels.

Referring to FIG. 21A, an implantable IC sensor 220B that detects fattydeposits and tissue growth inside the lumen of the stent 232 isillustrated as being disposed within the body of the stent 232, coupledto a pair of dielectric sensing filaments 234. The implantable IC sensor220B detects fatty deposits and tissue ingrowth within the lumen of thestent by measuring the dielectric and/or resistive properties of anymaterial in contact with the sensing filaments 234, which are, e.g.,helically coiled around the inner surface of the stent 232, from aboutone end of the stent 232 to its opposite longitudinal end.Alternatively, the sensing filaments 234 can be incorporated into thebody or wall of the stent 232 itself. For example, when the stent 232 isfabricated with a woven mesh, a portion of the mesh can be utilized formaking the dielectric and/or resistive measurement, while the remainderis used for a RF coupling coil.

In another embodiment, the sensing filaments 234 may be spatially morelimited to allow assessment of where blockage is occurring within thestent 232. A plurality of localized sensing filaments 234 may permitassessment of more than one area within the stent 232, by taking aseries of measurements and communicating the results of the series ofmeasurements to the attending physician. This may provide data relevantto determining what form of treatment is appropriate.

For measuring the dielectric properties, the implantable IC sensor 220Bis energized with power electromagnetically coupled from an externalsource into the RF coupling coil (not illustrated in FIG. 21A) of thestent 232 and produces signals indicative of tissue ingrowth that areelectromagnetically coupled to the external monitoring system throughthe RF coupling coil of the stent 232. In one embodiment, an RF signalat a frequency of from 10 to 100 MHz is applied to the sensing filaments234. At such frequencies, tissue has the properties shown in thefollowing Table 1. FIG. 21B illustrates an exemplary cross section of alumen 235 within the stent 232, showing the ingrowth of fatty tissue236, which is in contact with the sensing filaments 234.

TABLE 1 Tissue Type Relative Permittivity Resistivity (Ohm-cm) Fat 6 to20 2000 to 3000 Blood 80 to 160 80 to 90 Muscle 60 to 130 100 to 150

The permittivity of tissue is closely related to its water content.Water has a relative permittivity of about 80. Since fat and fattydeposits of the type found inside blood vessels contain much less waterthan other tissue types, the permittivity of fat is much lower than thatof muscle or blood. The wall of a blood vessel is muscular and highlyperfused and will therefore have a much higher permittivity than a fattydeposit. Similarly, fatty deposits have a much higher resistivity thaneither blood or muscle. Therefore, a measurement of the dielectricand/or resistive properties of tissue inside the stent 232 candifferentiate fatty deposits from either blood or muscular tissueingrowth into the lumen. The measurement can include a determination ofcapacitance, resistance or a combination of the two.

Further information can be obtained from the frequency dependence of thecapacitance and resistance measured inside a stent lumen. For example,blood has a relatively flat resistivity vs. frequency characteristiccurve, compared to that of muscle.

FIG. 22 illustrates a stent graft (or spring graft) 260 that includesembodiments of the present invention. The stent graft 260 differs from aconventional synthetic graft in the method of delivery. Conventionalgrafts are installed surgically, while stent grafts 260 are installedusing an endovascular delivery system. The entire stent graft 260 mustbe collapsible onto a delivery catheter (not shown). At a minimum, thestent graft 260 comprises a synthetic graft section 264 with anexpandable stent 262 or 266 disposed at one or both ends. The stents 262and 266 retain the synthetic graft section 264 in position. Some stentgrafts 260 have stents 262 and 266 disposed along the entire length ofthe synthetic graft section 264, and some may include metal hooks at oneor both ends to firmly attach the synthetic graft section 264 to thevessel wall.

The stent graft 260 is of a type that is used to repair arteries near abifurcation of the artery into two small branches 268 and 270. However,it should be noted that the present invention can be used with almostany type of stent graft and is not in any way limited to the bifurcatedtype shown in the figure. The TALENT spring graft system available fromWorld Medical Manufacturing is similar to the stent graft 260. The term“spring graft” is used with this type of stent graft 260 because thestent portions 262 and 266 may be self-expanding, comprising Nitinolsprings acting as stents 262 and 266 that are embedded into polyester(DACRON™) or PTFE synthetic graft section 264. The larger diameteraortic section typically comprises DACRON and the smaller branchportions typically comprise PTFE. The material comprising the syntheticgraft section 264 is stitched to the Nitinol stents 262. Although aNitinol stent is normally self-expanding, a balloon (not shown) may beincluded in the delivery system to perform one or more functions,including expansion of the stent 262, placement at the desired location,flow occlusion and straightening blood vessels to aid advancement of theassembly to the desired location. Electrically insulating ceramic joints276 couple sections of each stent 262 and 266 to break any current loopthat could reduce the efficiency of the RF coupling coil. An insulatedwire 272 is wound around the outside of the graft 264 and, in oneembodiment, is formed of kinked or zigzag wire to enable expansion ofthe graft 264. The wire 272 is coupled to a sensor/electronic circuit274. Stent grafts suitable for use in the embodiment shown in FIG. 22are made by Sulzer Vascutek and W. L. Gore. The ANEURX stent graft fromMedtronic, and the WALLGRAFT stent graft from Medivent-Schneider, whichincludes a woven mesh stent within its wall, are also suitable for thisembodiment.

Description of Therapeutic Transducers

A variety of therapeutic transducers may be implanted that areresponsive to and/or powered by the signals coupled into the implantableelectronic circuits of FIGS. 1 through 6. One class of therapeutictransducers 44-46 provide utility by enabling localized delivery oractivation of specific drugs for specific purposes. Two distinctapplications where therapeutic transducers implanted within endoluminalimplants provide therapeutic advantages are as adjunctive therapy and asprimary therapy.

In adjunctive therapy, the therapeutic transducer is intended to realizelocalized drug activation and delivery in the vicinity of the stent orstent graft. This could be to maintain flow capability through the lumenby reducing restenosis due to new deposits of atherosclerotic materialor to inhibit tissue ingrowth. Alternatively, in at least some cases,the same therapeutic transducer may aid in reducing thrombosis that iscausing lumen blockage by activating appropriate drugs.

In primary therapy, the stent with the therapeutic transducer isimplanted specifically to provide local drug activation and delivery totissue in the vicinity of and downstream from the stent. For example, astent could be implanted in an artery that feeds blood to a tumor site.Systemically administered chemotherapeutic agents that are not toxicuntil activated may be activated during passage through the stent byenergy provided by the therapeutic transducer. The blood containing theactivated drug then proceeds downstream to the tumor site to locallyadminister the activated drug. This approach can provide significantlygreater drug concentrations at the tumor site than are obtainedsystemically. Similarly, other drugs used to treat a variety of diseasesmay be locally activated at the region of interest. In some cases,modified genetic material may be locally concentrated in response totherapeutic transducer activation.

One advantage to localized activation or delivery of drugs is that theside effects associated with the drugs may be reduced by only providingthe drug at the site requiring treatment. This is advantageous in manysituations, including chemotherapy, where the drugs are toxic or mayhave other potentially detrimental side effects.

For example, drug activation phenomena have been reported usingultrasound to break precursor substances down into drug molecules andother by-products. In this case, one or more of the transducers 44-46 ofFIGS. 1 through 6 are ultrasonic transducers, several of which aredescribed with respect to FIGS. 13 through 18. Sonochemical activationof hematoporphyrin for tumor treatment is described by S. I. Umemura etal. in Sonodynamic Activation of Hematoporphyrin: A Potential ModalityFor Tumor Treatment, published in the 1989 IEEE Ultrasonics SymposiumProceedings, IEEE cat. no. 0090-5607/89/0000-0955, pp. 955-960.Ultrasonic potentiation of adriamycin using pulsed ultrasound isdescribed by G. H. Harrison et al. in Effect Of Ultrasonic Exposure TimeAnd Burst Frequency On The Enhancement Of Chemotherapy By Low-LevelUltrasound, published in the 1992 IEEE Ultrasonics SymposiumProceedings, IEEE cat. no. 1051-0117/92/0000-1245, pp. 1245-1248.Similarly, increased toxicity of dimethlyformamide has been reported inconjunction with ultrasound by R. J. Jeffers et al. in EnhancedCytotoxicity Of Dimethylformamide By Ultrasound In Vitro, published inthe 1992 IEEE Ultrasonics Symposium Proceedings, IEEE cat. no.1051-0117/92/0000-1241, pp. 1241-1244.

Sonodynamic activation at one or more specific body sites to providelocal drug delivery is possible when one or more of the transducers44-46 of FIGS. 1 through 6 are designed to provide suitable ultrasonicsignals and are implanted at the locations where drug activationprovides therapeutic benefits. Sonodynamic effects are nonlinear effectsassociated with the peak compression and expansion portions of the wavecycle; at lower frequencies, the time that the peak portions of the wavehave to act is greater. For this reason, lower frequencies are preferredin some embodiments. Other embodiments increase peak forces by combiningtwo or more ultrasonic waves. Several such transducers are described inconnection with FIGS. 23 and 24 below.

FIG. 23 illustrates an ultrasonic transducer configuration 278integrated with a stent 279. The ultrasonic transducer configuration 278is specifically designed to provide sonodynamic therapy via standingwaves providing sonochemical activation of blood-borne drug precursors.This occurs in response to control signals coupled from the implantableelectronic circuitry of FIGS. 1 through 6 by lines 281. The ultrasonictransducer configuration 278 is useful where local drug activation isdesired in order to deliver the drug to the vessel having the stent 279therein. The ultrasonic transducer configuration 278 is also useful whenthe downstream vasculature or an organ or tumor that is supplied bloodvia the downstream vasculature is the intended target for the activateddrug.

The stent 279 includes an implantable ultrasonic transducer 280 on afirst surface and a device 282 on a second surface. The device 282 maybe either another ultrasonic transducer similar to the transducer 280 oran acoustic reflector. The ultrasonic transducer 280 may be coupled toimplantable electronic circuits using any of the approaches described inconnection with FIGS. 1 through 6. In one embodiment, the layerstructure described in connection with FIG. 17 is applicable to thetransducer 280. The standing acoustic wave, represented by the dashedparallel lines in FIG. 23, that is realized between the transducer 280and the device 282 results in greater peak acoustic field strength for agiven input energy level, which increases the rate of sonochemical drugactivation and reduces the power levels required for sonochemical drugactivation. Peak acoustic pressure increases of three- to five-fold arelikely in most clinical settings.

The piezoelectric material forming the transducer 280 may comprisepiezoelectric plastic materials such as PVDF, P(VCN/VAc) or P(VDF-TrFE),available from AMP Sensors of Valley Forge, Pa., or any of thepiezoelectric ceramics, e.g., lead zirconium titanate. In oneembodiment, PZT-4 material available from Morgan-Matroc of Bedford, Ohioprovides high electroacoustic coupling and low acoustic losses. Inanother embodiment, the piezoelectric plastic P(VDF-TrFE) provides highelectroacoustic coupling and low acoustic losses.

The transducer 280 (and, when the device 282 is a transducer, the device282) may be of the type described, for example, with respect to FIGS. 13through 18, or may be a slab type ultrasonic transducer, or may besimilar to that shown and described in connection with FIG. 24,described below. In this application, the alignment between thetransducer 280 and the device 282 must be maintained in order topreserve parallelism of the surface of transducer 280 that surfaces thedevice 282 and the surface of the device 282 that faces the transducer280. It is also important to keep these surfaces opposed to each other,i.e., relative lateral motion of the transducer 280 and the device 282must be inhibited. The result of maintaining this alignment is to forman acoustic cavity analogous to an optical Fabry-Perot resonator.

FIG. 23 also shows biocompatible coatings 284 surrounding both thetransducer 280 and the device 282. The biocompatible coatings 284 areanalogous to the biocompatible outer coating 192 of FIG. 17. Thetransducer 280 may also include an acoustic backing analogous to theacoustic backing 194 of FIG. 17, disposed on the transducer 280 asdescribed in conjunction with FIG. 17. When an acoustic backing isemployed with the transducer 280 (or in the device 282), it is importantthat the surface of transducer 280 that faces the device 282 (and thesurface of the device 282 that faces the transducer 280) not be coatedwith the acoustic backing material.

When the device 282 is chosen to be an acoustic reflector, either a lowimpedance reflector (i.e., providing an acoustic reflection coefficientapproaching −1) or a high impedance reflector (i.e., providing anacoustic reflection coefficient approaching +1) may be employed.Low-density foams (e.g., analogous to the acoustic backing material 194of FIG. 17) or aerogels provide low acoustic impedances suitable for usein acoustic reflectors, while rigid bodies such as metals or ceramicsprovide high acoustic impedances suitable for use in acousticreflectors. Setting the thickness T_(R) of the acoustic reflector to bean odd multiple of one quarter of an acoustic wavelength, as measured inthe acoustic reflector material, increases the reflection coefficient ofthe acoustic reflector.

Alternatively, methods for localized delivery of medication includeencapsulation of medications in delivery vehicles such as microbubbles,microspheres or microballoons, which may be ruptured to locally releasethe medications via localized energy provided by implanted transducers.In some embodiments, the delivery vehicles may include magneticmaterial, permitting the delivery vehicles to be localized via anapplied magnetic field, as described in U.S. Pat. No. 4,331,654 entitledMagnetically-Localizable, Biodegradable Lipid Microspheres.

In one embodiment, the device 282 is formed from a magnetic ceramic or amagnetic metal alloy, and is also capable of acting as an efficientacoustic reflector. This embodiment allows localization of magneticdelivery vehicles via the static magnetic field associated with thedevice 282, followed by insonification of the delivery vehicles whenappropriate via ultrasound emitted by the transducer 280 in response tosignals from any of the implantable electronic circuits shown in FIGS. 1through 6. As used herein, the term “insonify” means “expose to sound”or “expose to ultrasound”; “insonification” is used to mean exposure tosound or ultrasound. Insonification of delivery vehicles can providelocalized heating, can rupture microbubbles to locally release drugs ordrug precursors contained in the delivery vehicles or can triggersonodynamic activation of drug precursors that are blood-borne or thatare released when the delivery vehicles rupture. Microbubbles containingantistenotic agents are described, for example, by R. L. Wilensky et al.in Microspheres, Semin. Intervent. Cardiol., 1: 48-50, 1996.Microbubbles of various compositions and filled with various drugs aredeveloped and manufactured by ImaRx Pharmaceutical Corp. of Tucson Ariz.An advantage that is provided by use of an implanted permanent magnetfor localization of magnetic delivery vehicles in this embodiment andothers is that permanent magnets do not require a rechargeable energysource in order to function. In some embodiments, this can provide a wayof reducing power needs from the RF-to-DC power supply 32 of FIGS. 1through 6.

The frequency of the ultrasound from the therapeutic transducer can bevaried to enhance or to reduce cavitation resulting from the ultrasoundemitted from the transducer. Suppression of cavitation via frequencymodulation is described in U.S. Pat. No. 5,694,936 entitled “UltrasonicApparatus For Thermotherapy With Variable Frequency For SuppressingCavitation.” Methods for suppression or enhancement of cavitation aredescribed in U.S. Pat. No. 4,689,986 entitled “Variable FrequencyGas-Bubble-Manipulating Apparatus And Method.” Enhancing cavitation toenhance sonodynamic activation, rupture of microspheres, microballoonsor microbubbles, to locally heat tissue or to destroy tissue is possibleby causing the frequency of the emitted ultrasound to decrease withtime. On the other hand, cavitation may be decreased by causing thefrequency of the emitted ultrasound to increase with time. This may beused to limit tissue damage while still supplying sufficient ultrasoundto accomplish, e.g., a diagnostic purpose.

Sonodynamic activation of drugs or sonically-induced delivery vehiclesrupture may occur at reduced power levels when properly-phased collinearacoustic signals at two different frequencies are provided. This effecthas been shown to be particularly advantageous when one signal is at afrequency that is the second harmonic of the other signal and the twosignals have an appropriate phase relationship. Increased tissue damagefor a given intensity of ultrasound has also been reported by S. I.Umemura in Effect Of Second-Harmonic Phase On Producing SonodynamicTissue Damage, published in the 1996 IEEE Ultrasonics SymposiumProceedings, IEEE cat. no. 0-7803-3615-1/96, pp. 1313-1318. Sonochemicalactivation of a gallium-deuteroporphyrin complex (ATX-70) at reducedtotal power density by use of properly phased signals comprising a firstsignal and a second signal at twice the frequency of the first signal isdescribed by S. I. Umemura et al. in Sonodynamic Approach To TumorTreatment, published in the 1992 IEEE Ultrasonics Symposium Proceedings,IEEE cat. no. 1051-0117/92/0000-1231, pp. 1231-1240. An example of atransducer that is designed to provide for transduction of twoultrasonic signals, one of which may be the second harmonic of theother, is now described with reference to FIG. 24.

FIG. 24 illustrates an embodiment of a dual frequency ultrasonictransducer 290. The dual frequency transducer 290 is designed to providetwo different frequencies of collinearly propagating ultrasound, whereone of the frequencies may be the second harmonic of the fundamentaltransducer frequency, when supplied with suitable electrical signals.The phases of the two signals may be adjusted by the implantableelectronic circuit of FIGS. 4 through 6 and this may be in response tosignals from the power supply and patient monitoring console 101 of FIG.12. The dual frequency transducer 290 comprises a disc 292 ofpiezoelectric material, poled, for example, as indicated by directionarrow 298. The disc 292 has a diameter D and a thickness TX. Electrode294 and electrode 296 are formed on opposed surfaces of the disc 292 asdescribed in conjunction with the rear and front electrodes 196 and 200of FIG. 17 above.

In one embodiment, the diameter D is chosen to provide the desiredfundamental transducer frequency via radial mode coupling, while thethickness T_(X) is chosen to provide the second harmonic of thefundamental transducer frequency via thickness mode coupling. In thiscase, the diameter to thickness ratio D/T_(X) may be approximately 2:1.Conventional mode charts provide more precise ratios for a variety ofmaterials. The radial mode comprises radial particle motion primarilyinto and out from the center of the disc, i.e., perpendicular to thedirection arrow 298, and symmetric about a cylindrical axis of the disc292. The surfaces of the disc 292 exhibit longitudinal motion (i.e.,parallel to the direction arrow 298) in response to the radial modeoscillation because of the Poisson's ratio of the material. Thethickness mode comprises particle motion parallel to the direction arrow298. As a result, acoustic energy propagating in the same direction atboth frequencies may be coupled out of the disc 292 via the surfaces onwhich the electrodes 294 and 296 are formed. In some embodiments, theacoustic radiating surface emitting the ultrasound does not include anelectrode 294 or 296. For example, electrodes may be disposed on thesidewalls, with ultrasound being emitted from the planar surfaces.

In another embodiment, the radial mode providing ultrasound at thefundamental transducer frequency may be chosen to be a harmonic of thelowest radial mode of the transducer 290. The transducer 290 may then bedesigned to have a larger diameter D than is possible when the lowestradial mode corresponds to the fundamental transducer frequency. Thisallows a larger area to be insonified by both ultrasonic signals than isotherwise feasible.

In one embodiment, frequencies of 500 kHz and 1 MHz are chosen as thetwo output frequencies for the dual frequency transducer 290. When thedisc 292 comprises lead zirconium titanate (PZT), the diameter D isabout 4 mm and the thickness T_(X) is about 2 mm. The resulting dualfrequency transducer 290 is small enough to be incorporated in animplantable device and yet also large enough to insonify a significantportion of the lumen of many blood vessels or stents.

In an alternative embodiment, a rectangular slab may be substituted forthe disc 292. In one embodiment, a lateral mode may then be used insteadof the radial mode associated with the disc 292 to provide the resonanceat the fundamental frequency, with the thickness mode providing theresonance at the second harmonic. Conventional mode charts are used toselect the ratios of the relevant dimensions.

Coating a cylindrical sidewall of the disc 292 and one of the electrodes294 and 296 with an acoustic isolator 300 (analogous to the acousticbacking 194 of FIG. 17) allows the other of the electrodes 294 and 296to serve as an acoustic radiator. Choosing the acoustic isolator 300 tohave a low relative dielectric constant reduces capacitive loading ofthe dual frequency transducer 290 by the patient's body, which, as notedabove, has a high relative dielectric constant (approaching 80) andwhich also includes conductive solutions. Coating the acoustic isolator300 with a grounded conductor 302, selecting the electrode 296 to be agrounded electrode and selecting the electrode 294 to be a drivenelectrode reduces unwanted radiation of electromagnetic signals from thetransducer 292. A thin biocompatible coating 304 (analogous to the outercoating 192 of FIG. 17) protects the dual frequency transducer 290 fromexposure to biological matter without preventing radiation of ultrasoundfrom the surface bearing the electrode 296.

Other types of localized therapy include coupling a thermally-activatedmedication to carrier molecules that have affinity to tumor tissue.Localized heating of the tumor tissue enables selective activation ofthe medication in the tumor tissue, as described in U.S. Pat. No.5,490,840 entitled Targeted Thermal Release Of Drug-Polymer Conjugates.Localized heating may be effected through ultrasound via an ultrasonictransducer, e.g., transducers 44-46 (FIGS. 1 through 6) implanted toallow insonification of the affected area. Higher acoustic frequenciesprovide shorter penetration depths, i.e., provide greater control overwhere the ultrasound and therefore the resultant heat is delivered.Additionally, heating is increased by ultrasonic cavitation in thepresence of microbubbles, microspheres or microballoons. Other methodsfor providing localized magnetic forces or heating includeelectromagnetic or resistive heating transducers 44-46 comprising coils.

FIG. 25 illustrates a coil 312 integrated into a stent 310. The coil 312comprises saddle-shaped wires 313 integrated into the stent 310. Thecoil 312 may be an electromagnetic transducer used to magneticallycapture delivery vehicles bearing drugs. Leads 314 couple the coil 312to an implantable control IC 315, which may comprise the implantableelectronic circuits of any of FIGS. 1 through 6. The implantableelectronic circuits of FIGS. 4 through 6 may provide advantages in thissituation because the frequency of the signal providing power to theimplantable electronic circuits may be different from the frequency ofthe signals to the transducers 44-46, such as the coil 312. This mayavoid a situation where the signals providing power to the implantableelectronic circuits also result in release of drugs in the vicinity ofthe RF coupling coil 30 that is receiving the electrical power.

When a suitable current, either AC or DC, is supplied via the leads 314,a magnetic field represented by flux lines 316 is generated. Themagnetic field captures magnetic delivery vehicles that have beenintroduced into the patient's bloodstream. The increased concentrationof delivery vehicles in the target vicinity can be used to provide localincreases in delivery of drugs contained in the delivery vehicles.

Microbubbles including medication may be localized via a magnetic fieldand ruptured via an oscillating magnetic field as described in U.S. Pat.No. 4,652,257 entitled Magnetically-Localizable, Polymerized LipidVesicles And Method Of Disrupting Same. Suitable magnetic fields may beprovided via application of RF or RF and DC electrical energy to thecoil 312. In these embodiments, one or more of the transducers 44-46 ofFIGS. 1 through 6 comprise the coil structure 312. In response tosignals coupled to the implantable electronic circuit, the transducer44-46 that is selected is activated and is supplied with current toeither trap the magnetic delivery vehicles so that they can be rupturedvia signals provided from another selected transducer 44-46 (e.g., anultrasonic transducer that ruptures microbubbles, microspheres ormicroballoons via cavitation), or an oscillating magnetic field may besuperposed on the magnetic fields generated by the coil 312 used to trapthe delivery vehicles.

Referring again to FIG. 25, in another embodiment, a permanent magnet311 may be included on or in the stent 310 to provide a static magneticfield for localization of magnetic delivery vehicles. An oscillatingmagnetic field may then be provided via signals supplied to the coil 312to rupture the delivery vehicles under the control of the implantableelectronic circuit of any of FIGS. 1 through 6, where the coil 312 actsas one of the transducers 44-46. These embodiments may reduce powerrequirements for the implantable control IC 315 while retaining externalcontrol over when the drug or drug precursor is released via signalsfrom the power supply and patient monitoring console 101 of FIG. 12.Other types of coils, e.g., analogous to the RF coupling coils 30B, 30Cor 30D of FIGS. 7 through 10, or 121 of FIGS. 11A and 11B, may also beused instead of the RF coupling coil 312.

FIG. 26 illustrates another embodiment of a coil 312A integrated into astent 310A. The coil 312A is analogous to the coil 312 of FIG. 25, butis shaped as a cylindrical coil rather than as a saddle-shaped spiral.Leads 314A couple wires 313A comprising the coil 312A to an implantablecontrol IC 315A, which is analogous to the implantable control IC 315 ofFIG. 25. When a suitable current, either AC or DC, is supplied via theleads 314A, a magnetic field represented by flux lines 316A isgenerated. The coil 312A may be used to capture magnetic deliveryvehicles that have been introduced into the patient's bloodstream.

In other embodiments, the coils 312 or 312A may form resistive heatingtransducers comprising a resistive material and may, if desired, bewound with bifilar wire to prevent them from acting as electromagnets orRF coupling coils. In another embodiment, the coils 312 or 312A may beheated directly by magnetic fields inducing current in the coils 312 or312A, or, the body of the stent 310A may form a resistive heatingtransducer that is heated via magnetically-induced currents.

Stents are typically fashioned from metals that are biocompatible, suchas titanium alloys (e.g., Nitinol, a nickel titanium alloy), stainlesssteel (e.g., 316L), platinum/iridium alloys or tantalum. All of thesematerials are suitable for fashioning a stent that is to be directlyheated by RF-induced eddy currents (such stents would not include slotssuch as slot 118, FIG. 11A, or insulating couplings such as 119, FIG.11A, or 146, FIG. 11B), however, titanium and Nitinol have the highestelectrical resistivity, while platinum/iridium and tantalum have thelowest electrical resistivity. When a stent body is to be directlyheated by induced eddy currents, titanium or Nitinol may presentadvantages.

When a RF coupling coil is to be fashioned from these materials, thoseapplications with higher power requirements may favor the materials withthe lower resistivities.

When a current is passed through coils analogous to RF coupling coils312 or 312A but comprising resistive material, or through a stent bodyas eddy currents, a local temperature rise is produced. This localtemperature rise may be employed to rupture microbubbles having amelting point slightly above normal human body temperatures. One systemusing microbubbles having a controlled melting point to facilitaterupture of the microbubbles at predetermined localized areas within apatient's body is described, for example, in U.S. Pat. No. 4,558,690entitled Method Of Administration Of Chemotherapy To Tumors. Thelocalized heating may be provided by a structure similar to thecylindrical RF coupling coil 30A of FIG. 7, the woven mesh coils 30B and30C of FIGS. 8 and 9, the saddle RF coupling coil 30D of FIG. 10, the RFcoupling coil 121 of FIGS. 11A and 11B, the coil 312 of FIG. 25 or thecoil 312A of FIG. 26, with the conductors of the coils comprising asuitably resistive material such as nichrome wire. The heating may besupplied directly by RF excitation of the coils 30A through 30D or 121,or it may be effected via the implantable electronic circuits of FIGS. 1through 6. This may be in response to signals from the power supply andpatient monitoring console 101 of FIG. 12. Additionally, deliveryvehicles such as microbubbles, microspheres or microballoons canincrease localized heating of tissue via rupture of the deliveryvehicles caused by localized application of ultrasound, as discussed,for example, in Technical Report: Drug And Gene Delivery, Jul. 2, 1997,ImaRx Pharmaceutical Corp.

Transducers may be employed to facilitate drug penetration through thewall of a stent or stent graft and into the surrounding vasculature viasonophoresis, i.e., ultrasound enhancement of drug penetration into bodytissues, or via iontophoresis, i.e., electrical field enhancement ofdrug penetration into body tissues, when suitable transducers areincluded in the stent or stent graft.

Methods and apparatus for localized drug delivery via sonophoresis orphonophoresis are described in U.S. Pat. No. 4,484,569 entitledUltrasonic Diagnostic And Therapeutic Transducer Assembly And Method ForUsing, U.S. Pat. No. 5,016,615 entitled Local Application Of MedicationWith Ultrasound and U.S. Pat. No. 5,267,985 entitled Drug Delivery ByMultiple Frequency Phonophoresis. These patents generally discusstransdermal delivery of medication to an affected area and note that useof more than one frequency of ultrasonic energy is beneficial in somesituations.

An iontophoretic catheter for drug delivery is described inIontophoretic Drug Delivery System, by R. G. Welsh et al., Semin.Intervent. Cardiol., No. 1, pp. 40-42 (1996). The system uses amicroporous membrane enclosing a drug solution and a drug deliveryelectrode. A reference electrode is coupled to the biological tissue ata site that is separate from the drug delivery electrode. The referenceand drug delivery electrodes are coupled to a power supply that providesan electrical potential between the two electrodes. Cationic drugs movefrom the anode towards the cathode, while anionic drugs move from thecathode towards the anode, with the rate being generally proportional tothe current. Control over localized drug delivery is effected viacontrol of the current and the duration of the current from the drugdelivery electrode. One application is for delivery of antirestenoticagents.

Other uses of iontophoresis are described in U.S. Pat. No. 4,383,529entitled Iontophoretic Electrode Device, Method and Gel Insert and U.S.Pat. No. 4,416,274 entitled Ion Mobility Limiting IontophoreticBioelectrode. These generally describe iontophoretic apparatus forlocalized transdermal drug delivery. Catheters adapted to providelocalized iontophoretic drug delivery are described in U.S. Pat. No.4,411,648 entitled Iontophoretic Catheter Device, and U.S. Pat. No.5,499,971 entitled Method for Iontophoretically Delivering Drug AdjacentTo A Heart. These discuss specific problems that are most readilyaddressed via localized drug delivery, including treatment of vascularregions to reduce restenosis following PTCA, drug delivery to tumorsites and techniques for iontophoretically delivering drugs in thevicinity of the heart without inducing arrhythmia due to electricalstimulation of heart muscles and nerves. In one embodiment, this iseffected together with provision of electrical fields effective inproviding drug transport by chopping a DC potential difference at a rateof between 5 and 15 kHz or by providing an asymmetric AC waveform thatis in this frequency range. These techniques are necessary because thecurrent being used for iontophoresis travels through a significant andsomewhat unpredictable amount of body tissue that may well includemuscles and nerves associated with the heart.

These concepts become more powerful when combined with the implantabletransducers 44-46 of FIGS. 4 through 6 for providing the energy tolocally deliver or locally activate the medications. An example of aniontophoretic transducer is described in conjunction with FIG. 27 below.

FIG. 27 illustrates an embodiment of an iontophoretic system 320 forlocal drug delivery in the vicinity of an implanted stent 322. Theiontophoretic system 320 includes an implantable control IC 324, whichmay be coupled to the stent 322. The implantable control IC 324 iscoupled via wires 326 to a first electrode 328 and to a second electrode330. The first 328 and second 330 electrodes are insulated from thestent 322 when the stent 322 comprises conductive material, unless thestent 322 comprises one of the electrodes 328 and 330. The first 328 andsecond 330 electrodes comprising an iontophoretic transducer may bedisposed on the exterior of the stent 322 (as illustrated), on theinterior of the stent 322, or may be disposed such that one is insidethe stent 322 and the other is external to the stent 322.

A potential difference is established between the first 328 and second330 electrodes by the implantable control IC 324 in response to signalscoupled from outside the patient's body, via a RF coupling coil (notillustrated) as discussed above. The potential difference causes sometypes of drugs to migrate from one of the electrodes 328 and 330 towardsthe other, according to the polarity of the potential difference and thespecific nature of the drug. This effect may be used to providelocalized drug therapy, for example, to the wall of the vessel (notillustrated) into which the stent 322 is implanted. For example,systemically-administered drugs may be selectively transported from theblood into the vasculature surrounding a stent 322 to provide increasedlocal concentrations of antistenotic agents.

One advantage of this technique is that the currents produced by theiontophoretic system 320 are extremely localized, i.e., aresubstantially confined to the area between the electrodes 328 and 330and immediately surrounding tissues. This obviates some of the problemsthat have been encountered with iontophoretic systems that use areference electrode that is placed at a body location remote from thedrug delivery electrode, e.g., a catheterized drug delivery electrodeused in conjunction with an externally-applied reference electrode.Accordingly, the iontophoretic system 320 may employ a DC voltage toeffect iontophoretic drug delivery to parts of the body that cannotsafely be treated via a catheterized system using DC for iontophoreticdrug delivery. This is advantageous in improving the efficiency of drugdelivery and in reducing exposure of other portions of the body to theelectrical currents being employed for iontophoresis. One area wherethis may provide advantages, depending on stent placement and otherfactors, is in treating restenosis of cardiac blood vessels followingstent insertion as a part of a PTCA treatment. A stent 322 intended forthis purpose may also include sensors providing signals indicative ofblood flow through the stent and therefore capable of providing dataindicative of blockage as it develops. Additionally, the stent 322including iontophoretic electrodes 328 and 330 may also be used toenhance localized delivery of drugs that are activated via therapeutictransducers coupled to the stent 322 or that are included in thevasculature upstream of the stent 322.

Another method for localized drug activation uses light supplied by anoptical transducer, where the light is of the appropriate wavelength andintensity to break precursor molecules down into drugs. U.S. Pat. No.5,445,608 entitled Method And Apparatus For Providing Light-ActivatedTherapy, describes a photodynamic therapy achieved by photoactivation ofsuitable optically active drugs. As described in this patent, the drugsare activated via catheterized light emitters inserted at the site to betreated and providing light at the wavelength required in order toactivate the drugs and at the location where the activated drugs areneeded for therapeutic purposes. Examples of precursor substances thatcan be optically activated by being broken down into drug moleculesinclude long-chain cyanine dyes, dimers of phthalocyanine dyes andporphyrin compounds. A wide selection of solid state light sourcesincluding laser diodes and light emitting diodes is commerciallyavailable from a variety of vendors, including Motorola of Phoenix,Ariz. Laser diodes or light emitting diodes may be employed astransducers 44-46 in any of the systems shown in FIGS. 1 through 6 toprovide light for photoactivation of drugs within a patient's body viasignals from the implantable electronic circuit in response to signalstransmitted from the power supply and patient monitoring console 101 ofFIG. 12.

FIG. 28 illustrates an embodiment wherein light emitting or opticaltransducers 338 are coupled to a stent 336. The light emittingtransducers 338 may comprise light emitting diodes having an appropriatewavelength or may comprise diode lasers. The light emitting transducers338 may be coupled in series via lines 340, as shown in FIG. 28, or maybe coupled in parallel. When the light emitting transducers 338 arecoupled in series, one disadvantage is that catastrophic failure of oneof the light emitting transducers 338 that causes the failed lightemitting transducer 338 to fail to pass enough current for lightemission may also prevent the remainder of the light emittingtransducers 338 from operating.

The light emitting transducers 338 are coupled via lines 342 to animplantable control IC 344, which is in turn coupled to a RF couplingcoil (not illustrated in FIG. 28) that provides energy and controlsignals. The light emitting transducers 338 may be disposed on theoutside of the stent 336, as shown, or on the inside of the stent 336 orboth as required for a given application.

The transducers 44-46 of FIGS. 1 through 6 may concentrate or activatemedications by supplying heat, via resistive processes orinsonification, or may employ light, magnetic fields or electricalfields for localized drug delivery or activation. The ultrasonictransducer 290 of FIG. 24 is, among other ultrasonic transducers, alsosuited to increasing drug penetration of drugs via sonophoresis into,e.g., tumors or vascular walls via an implantable electronic circuitsuch as any of those shown in FIGS. 4 through 6.

An example of an application for the systems described above occurs inthe situation where a stent is implanted to correct a stenosis or torepair an aneurysm in a blood vessel. Over time, tissue ingrowth at theends of the stent can lead to stenosis, which can lead to thrombusformation. Thrombosis threatens the viability of the stent, and mayrequire aggressive intervention using surgery or drugs. It is veryundesirable to have to surgically resolve this situation if there is aviable alternative approach for relieving the blockage. One approach isto infuse the patient with thrombolytic drugs. This may lead tohemorrhagic consequences in other parts of the body, especially if thepatient has, for example, recently had surgery. One approach to reducingthe amount of thrombolytic drugs required to resolve thromboses in vitrois described in Prototype Therapeutic Ultrasound Emitting Catheter ForAccelerating Thrombolysis, J. Ultrasound Med. 16, pp. 529-535 (1997). Inthis study, urokinase alone as a fibrinolytic agent was compared tourokinase in the presence of ultrasonic energy, with the latter showingmarked improvement in the degree of fibrinolysis of artificial bloodclots in glass tubes.

When, however, the stent includes a transducer, such as an ultrasonictransducer, coupled to the implantable electronic circuit of any ofFIGS. 1 through 6, the introduction of a thrombolytic drug into thebloodstream of the patient can be followed by generation of ultrasoundwithin the stent via the transducer and under the control of anattending physician. This allows the thrombolytic drug, e.g., urokinase,streptokinase or tissue plasminogen activator, to be activated at thesite of the thrombus and under the control of the attending physician,reducing the probability of hemorrhagic consequences at portions of thepatient's body remote from the site being treated. It also enables rapidonset of treatment, which can be critical in some situations, e.g., inthe event of heart attack or stroke induced via thrombolysis, and mayobviate invasive surgery in the event that the therapeutic transducerhas already been implanted in a prior procedure.

Additionally, when flow or pressure sensors such as are described withrespect to FIGS. 13 through 16 or 18 are also included with the stentwhen the stent is implanted and these are also coupled to theimplantable electronic circuits of any of FIGS. 2 through 6, theattending physician may be able to obtain information that is indicativeof graft condition. This can allow the physician to more readilydetermine if the condition is treatable without resorting to invasiveevaluation and intervention. Monitoring during non-invasive treatment,e.g., local drug activation, accomplished through use of an implantedblood velocity or blood pressure transducer, may allow assessment of theprogress of thrombolysis that may, in turn, permit successfulnoninvasive treatment without incurring undue risk to the patient.

Further, when stents are implanted to relieve stenosis, restenosis dueto tissue ingrowth tends to occur within the first 6 months followingangioplasty, with the greatest loss of luminal diameter occurringbetween the first and third month. Detection of tissue growth can bedetermined via pressure sensors as described above or via incorporationof the dielectric sensing filaments 234 and the implantable IC sensor220B of FIGS. 21A and 21B. When the ultrasonic transducers, such asthose of any of FIG. 13-18, 23 or 24, are included in the upstream sideof an implanted stent, precursor drugs activated sonodynamically maylocally provide antistenotic agents such as colchicine, heparin,methotrexate, angiopeptin or hirudin to relieve or reduce restenosiswithout requiring systemic administration of the drugs. Alternatively,delivery vehicles ruptured via ultrasound may provide localized deliveryof antistenotic agents. This provides a way of controlling restenosis onan as-needed basis as determined via the benefit of diagnostic data,under the control of a physician, and without requiring anesthesia orsurgery. An advantage associated with at least some of the therapeutictransducers described herein is that they are not necessarily specificto one drug or condition. For example, ultrasonically activated therapyprovides advantages in treatment of both restenosis and thromboses,either of which may threaten viability of an implanted stent.

From the foregoing it will be appreciated that, although specificembodiments of the invention have been described herein for purposes ofillustration, various modifications may be made without deviating fromthe spirit and scope of the invention. Accordingly, the invention is tobe understood broadly and is not limited except as by the appendedclaims.

1. A method comprising: coupling, via a magnetic signal, a signal to atherapeutic transducer contained in an endoluminal implant; activatingsaid therapeutic transducer in response to said magnetic signal, theactivating including ultrasonically activating a drug coupling adiagnostic signal from a diagnostic transducer contained in saidendoluminal implant to an implantable electronic circuit that is coupledto said endoluminal implant; transmitting said diagnostic signal from aRF coupling coil that is electrically coupled to said implantableelectronic circuit; and receiving said diagnostic signal at a locationoutside of a patient's body within which said endoluminal implant isimplanted wherein activating said therapeutic transducer includesactivating said therapeutic transducer in response to said diagnosticsignal.
 2. A method comprising: receiving, at a location outside apatient's body, a diagnostic signal from a diagnostic transducer coupledto an endoluminal implant disposed within a patient's body;transmitting, from said location outside said patient's body, atherapeutic signal in response to receiving said diagnostic signal; andactivating a therapeutic transducer that is coupled to said endoluminalimplant in response to said therapeutic signal, the activating includingultrasonically activating a drug.
 3. The method of claim 2 whereinreceiving a diagnostic signal includes receiving a diagnostic signaldescribing fluid flow through a lumen of said endoluminal implant. 4.The method of claim 3 wherein activating a therapeutic transducerincludes providing, within said lumen, energy for activating a drugprecursor.
 5. The method of claim 2, further comprising: transmitting,from said location outside said patient's body, a power signal forproviding electrical power to implantable electronic circuitry coupledto said endoluminal implant; and receiving said power signal by a RFcoupling coil disposed within said patient's body and electricallycoupled to said implantable electronic circuitry.
 6. The method of claim2, further comprising transmitting, from said location outside saidpatient's body, a power signal via a hardwired connection extending fromsaid location outside said patient's body to said implantable electroniccircuitry, said power signal for providing electrical power toimplantable electronic circuitry coupled to said endoluminal implant. 7.The method of claim 2 wherein receiving a diagnostic signal includes:receiving a first diagnostic signal describing fluid pressure at a firstend of a lumen of said endoluminal implant; and receiving a seconddiagnostic signal describing fluid pressure at a second end of saidlumen of said endoluminal implant.
 8. A method comprising: coupling, viaa magnetic signal, a signal to a therapeutic transducer contained in anendoluminal implant; activating said therapeutic transducer in responseto said magnetic signal, the activating including rupturing deliveryvehicles to locally deliver a drug coupling a diagnostic signal from adiagnostic transducer contained in said endoluminal implant to animplantable electronic circuit that is coupled to said endoluminalimplant; transmitting said diagnostic signal from a RF coupling coilthat is electrically coupled to said implantable electronic circuit; andreceiving said diagnostic signal at a location outside of a patient'sbody within which said endoluminal implant is implanted whereinactivating said therapeutic transducer includes activating saidtherapeutic transducer in response to said diagnostic signal.
 9. Amethod comprising: receiving, at a location outside a patient's body, adiagnostic signal from a diagnostic transducer coupled to an endoluminalimplant disposed within a patient's body; transmitting, from saidlocation outside said patient's body, a therapeutic signal in responseto receiving said diagnostic signal; and activating a therapeutictransducer that is coupled to said endoluminal implant in response tosaid therapeutic signal, the activating including rupturing deliveryvehicles to locally deliver a drug.
 10. The method of claim 9 whereinreceiving a diagnostic signal includes receiving a diagnostic signaldescribing fluid flow through a lumen of said endoluminal implant. 11.The method of claim 10 wherein activating a therapeutic transducerincludes providing, within said lumen, energy for activating a drugprecursor.
 12. The method of claim 9, further comprising: transmitting,from said location outside said patient's body, a power signal forproviding electrical power to implantable electronic circuitry coupledto said endoluminal implant; and receiving said power signal by a RFcoupling coil disposed within said patient's body and electricallycoupled to said implantable electronic circuitry.
 13. The method ofclaim 9, further comprising transmitting, from said location outsidesaid patient's body, a power signal via a hardwired connection extendingfrom said location outside said patient's body to said implantableelectronic circuitry, said power signal for providing electrical powerto implantable electronic circuitry coupled to said endoluminal implant.14. The method of claim 9 wherein receiving a diagnostic signalincludes: receiving a first diagnostic signal describing fluid pressureat a first end of a lumen of said endoluminal implant; and receiving asecond diagnostic signal describing fluid pressure at a second end ofsaid lumen of said endoluminal implant.
 15. A method comprising:receiving, at a location outside a patient's body, a diagnostic signalfrom a diagnostic transducer coupled to an endoluminal implant disposedwithin a patient's body; transmitting, from said location outside saidpatient's body, a therapeutic signal in response to receiving saiddiagnostic signal; and activating a therapeutic transducer that iscoupled to said endoluminal implant in response to said therapeuticsignal, the activating including activating an ultrasonic transducer toinsonify a lumen of said endoluminal implant with a first ultrasonicsignal having a first frequency and a second ultrasonic signal having asecond frequency, wherein receiving a diagnostic signal includesreceiving a diagnostic signal describing fluid flow through a lumen ofsaid endoluminal implant, and wherein activating a therapeutictransducer includes providing, within said lumen, energy for activatinga drug precursor.
 16. A method comprising: receiving, at a locationoutside a patient's body, a diagnostic signal from a diagnostictransducer coupled to an endoluminal implant disposed within a patient'sbody; transmitting, from said location outside said patient's body, atherapeutic signal in response to receiving said diagnostic signal; andactivating a therapeutic transducer that is coupled to said endoluminalimplant in response to said therapeutic signal, the activating includingactivating an ultrasonic transducer to insonify a lumen of saidendoluminal implant with a first ultrasonic signal having a firstfrequency and a second ultrasonic signal having a second frequency,wherein said first and second ultrasonic signals are collinear whereinreceiving a diagnostic signal includes receiving a diagnostic signaldescribing fluid flow through a lumen of said endoluminal implant, andwherein activating a therapeutic transducer includes providing, withinsaid lumen, energy for activating a drug precursor.